1000 Sentences With "cofactor" | Random Sentence Generator

Plus, it kills two birds with one stone: Vitamin C is a cofactor of collagen production, so it also helps strengthen skin, minimizing fine lines in the process.

Cofactor Genomics has announced an $18 million Series A financing round led by Menlo Ventures, with participation from DCVC, Ascension Ventures, iSelect, Y Combinator, Wilson Sonsini Goodrich & Rosati and Stanford.

Since then, Cofactor Genomics has secured CAP/CLIA accreditation, validated and launched two initial products: Pinnacle, which thumbs through nearly 600 RNA biomarkers associated with good drug response, and Paragon, which is an RNA-based immunophenotyping assay that can be broadly applied to cancer therapy.

Cortex is now home to about 325 companies, with names like CoFactor Genomics and Boundless, which have found a home in the Centre for Emerging Technologies, an incubator; the BioGenerator, an accelerator that works with startups for a short, intense time; TechShop, a workspace for prototyping; or another of the seven innovation centres.

He has also seemingly spent a lot of time looking at health care-related startups, with other investments in Notable Labs, a year-old, San Francisco-based personalized drug combination testing service for cancer patients; CoFactor Genomics, an eight-year-old, St. Louis, Mo.-based company that's building disease diagnostics using RNA (as opposed to DNA); and Call9, a year-old, Palo Alto-based telemedicine startup that calls doctors on demand.

Dr. David L. Heymann, chairman of the World Health Organization committee that recommended the declaration of the public health emergency, said in an interview last week that very tool — a case control study following two sets of pregnant women, some who had Zika and some who did not — was what his committee needed to prove whether Zika causes microcephaly, and whether it does so alone or requires a cofactor like a prior infection with dengue.

Molybdenum cofactor guanylyltransferase (, MobA, MoCo guanylyltransferase) is an enzyme with systematic name GTP:molybdenum cofactor guanylyltransferase. This enzyme catalyses the following chemical reaction: : GTP + molybdenum cofactor \rightleftharpoons diphosphate + guanylyl molybdenum cofactor Catalyses the guanylation of the molybdenum cofactor.

Molybdenum cofactor cytidylyltransferase (, MocA, CTP:molybdopterin cytidylyltransferase, MoCo cytidylyltransferase, Mo-MPT cytidyltransferase) is an enzyme with systematic name CTP:molybdenum cofactor cytidylyltransferase. This enzyme catalyses the following chemical reaction: : CTP + molybdenum cofactor \rightleftharpoons diphosphate + cytidylyl molybdenum cofactor Catalyses the cytidylation of the molybdenum cofactor.

Molybdenum cofactor sulfurtransferase (, molybdenum cofactor sulfurase, ABA3, HMCS, MoCo sulfurase, MoCo sulfurtransferase) is an enzyme with systematic name L-cysteine:molybdenum cofactor sulfurtransferase. This enzyme catalyses the following chemical reaction : molybdenum cofactor + L-cysteine + 2 H+ \rightleftharpoons thio-molybdenum cofactor + L-alanine + H2O This enzyme contains pyridoxal phosphate.

Molybdenum cofactor synthesis protein 2A and molybdenum cofactor synthesis protein 2B are a pair of proteins that in humans are encoded from the same MOCS2 gene.: MOCS2 molybdenum cofactor synthesis 2 These two proteins dimerize to form molybdopterin synthase.

Mutations in this gene are associated with heparin cofactor II deficiency. Heparin Cofactor II deficiency can lead to increased thrombin generation and a hypercoagulable state.

This pathway was modified in order to match the preferred reducing cofactor for the cyanobacteria. Example of how Cofactor Engineering can be used to engineer one pathway to influence another.

Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state.

The purple dashes are the hydrogen bonds involved. Top view of the enzyme. Cofactor Binding Site: The PLP cofactor is positioned in between the Beta-strands 7 and 10 of the large domain and lies on the large internal gap made between small and large domain. The cofactor is covalently bonded through a Schiff base linkage to Lys41.

It employs one cofactor, NADP+ in a direct oxidation mechanism.

Molybdenum cofactor sulfurase is an enzyme that in humans is encoded by the MOCOS gene. MOCOS sulfurates the molybdenum cofactor of xanthine dehydrogenase (XDH) and aldehyde oxidase (AOX1), which is required for their enzymatic activities.

Molecular oxygen and the copper ion are utilized to reoxidize the cofactor and yield another imine, producing hydrogen peroxide as a side product. Additional hydrolysis releases ammonia and the original cofactor, completing the catalytic cycle.

This enzyme participates in glycerolipid metabolism. It employs one cofactor, cobamide.

This enzyme participates in glycerolipid metabolism. It employs one cofactor, cobalamin.

This enzyme participates in sulfur metabolism. It employs one cofactor, manganese.

This enzyme participates in glutathione metabolism. It employs one cofactor, magnesium.

This enzyme participates in purine metabolism. It employs one cofactor, iron.

This enzyme participates in monoterpenoid biosynthesis. It employs one cofactor, heme.

This enzyme participates in tyrosine metabolism. It employs one cofactor, zinc.

This enzyme participates in tryptophan metabolism. It employs one cofactor, heme.

This enzyme participates in thiamine metabolism. It employs one cofactor, FAD.

This enzyme participates in glycerophospholipid metabolism. It employs one cofactor, FAD.

This enzyme participates in pyruvate metabolism. It employs one cofactor, tungsten.

This enzyme participates in lysine degradation. It employs one cofactor, cobamide.

This enzyme participates in aminosugars metabolism. It employs one cofactor, ATP.

This enzyme participates in glycerophospholipid metabolism. It employs one cofactor, adenosylcobalamin.

This enzyme participates in sphingolipid metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in taurine metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in phenylalanine metabolism. It employs one cofactor, pyridoxal phosphate.

An essential cofactor for ADCY2 is magnesium; two ions bind per subunit.

This enzyme participates in propanoate metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme is also called orcinol hydroxylase. It employs one cofactor, FAD.

This enzyme participates in biosynthesis of steroids. It employs one cofactor, glutathione.

This enzyme participates in cysteine metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in tyrosine metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in aminophosphonate metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in lysine degradation. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in biotin metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in tryptophan metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in lysine biosynthesis. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in lysine degradation. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in glutamate metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in methane metabolism. It employs one cofactor, thiamin diphosphate.

This enzyme participates in alkaloid biosynthesis i. It employs one cofactor, iron.

This enzyme participates in vitamin B6 metabolism. It employs one cofactor, FAD.

This enzyme participates in pentose phosphate pathway. It employs one cofactor, PQQ.

This enzyme participates in fatty acid metabolism. It employs one cofactor, PQQ.

This enzyme participates in 2,4-dichlorobenzoate degradation. It employs one cofactor, FAD.

This enzyme participates in pentose phosphate pathway. It employs one cofactor, FAD.

This enzyme participates in nucleotide sugars metabolism. It employs one cofactor, NAD+.

This enzyme participates in pentose phosphate pathway. It employs one cofactor, manganese.

Tubulin-specific chaperone E is a protein that in humans is encoded by the TBCE gene. Cofactor E is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state.

This enzyme participates in fructose and mannose metabolism. It employs one cofactor, NAD+.

This enzyme participates in selenoamino acid metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in glyoxylate and dicarboxylate metabolism. It employs one cofactor, iron.

This enzyme participates in beta-alanine metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in nucleotide sugars metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in alanine and aspartate metabolism. It employs one cofactor, FAD.

This enzyme participates in pyruvate metabolism. It employs one cofactor, nicotinamide D-ribonucleotide.

This enzyme participates in fructose and mannose metabolism. It employs one cofactor, FAD.

This enzyme participates in porphyrin and chlorophyll metabolism. It employs one cofactor, FAD.

This enzyme participates in arginine and proline metabolism. It employs one cofactor, FAD.

PODXL has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.

This enzyme participates in arginine and proline biosynthesis. It employs one cofactor, NAD+.

This enzyme participates in pentose phosphate pathway. It employs one cofactor, pyridoxal phosphate.

PLCB3 has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.

Molybdenum cofactor deficiency is a rare human disease in which the absence of molybdopterin – and consequently its molybdenum complex, commonly called molybdenum cofactor – leads to accumulation of toxic levels of sulphite and neurological damage. Usually this leads to death within months of birth, due to the lack of active sulfite oxidase. Furthermore, a mutational block in molybdenum cofactor biosynthesis causes absence of enzyme activity of xanthine dehydrogenase/oxidase and aldehyde oxidase.

This enzyme participates in c5-branched dibasic acid metabolism. It employs one cofactor, iron.

This enzyme participates in valine, leucine and isoleucine degradation. It employs one cofactor, FAD.

This enzyme participates in porphyrin and chlorophyll metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in alanine and aspartate metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, FAD.

This enzyme participates in glyoxylate and dicarboxylate metabolism. It uses Manganese as a cofactor.

This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, PQQ.

This enzyme participates in valine, leucine and isoleucine biosynthesis. It employs one cofactor, ascorbate.

This enzyme participates in c5-branched dibasic acid metabolism. It employs one cofactor, cobamide.

This enzyme participates in porphyrin and chlorophyll biosynthesis. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in c5-branched dibasic acid metabolism. It employs one cofactor, cobamide.

Defects in both copies of MOCS2 cause the molybdenum cofactor deficiency disease in babies.

This enzyme participates in tyrosine metabolism and alkaloid biosynthesis. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in tyrosine metabolism and nitrogen metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, pyridoxal phosphate.

In December of 2016, Liquidus, a Chicago based digital media/ad tech agency purchased CoFactor.

This enzyme participates in ascorbic acid and aldaric acid metabolism. It employs one cofactor, FAD.

This enzyme participates in alkaloid biosynthesis i. It employs one cofactor, heme- thiolate(P-450).

This enzyme participates in lysine biosynthesis and lysine degradation. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, pyridoxal phosphate.

Cofactor of BRCA1, also known as COBRA1, is a human gene that encodes NELF-B.

This enzyme participates in nitrogen metabolism and sulfur metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in cysteine metabolism and taurine metabolism. It employs one cofactor, pyridoxal phosphate.

Reaction mechanism of the flavin cofactor to catalyse the Baeyer-Villiger reaction in Baeyer-Villiger monooxygenase enzymes. In nature, enzymes called Baeyer- Villiger monooxygenases (BVMOs) perform the oxidation analogously to the chemical reaction. To facilitate this chemistry, BVMOs contain a flavin adenine dinucleotide (FAD) cofactor. In the catalytic cycle (see figure on the right), the cellular redox equivalent NADPH first reduces the cofactor, which allows it subsequently to react with molecular oxygen.

CDO contains a unique internal cofactor created by intramolecular thioether formation between Cys93 and Tyr157, which is postulated to participate in catalysis. When the protein was first isolated, two bands on agarose gel were observed, corresponding to the cofactor- containing protein and the unlinked "immature" protein, respectively. Crosslinking increases efficiency of CDO ten-fold and is regulated by levels of cysteine, an unusual example of protein cofactor formation mediated by substrate (feedforward activation).

The sulfonucleotide reductases are through to have all evolved from a common ancestor. The enzymes reduce adenosine-5'-phosphosulfate by nucleophilic attack to produce the sulfite product. This typically involves a cofactor (such as an iron-sulphur cluster), however the cofactor varies in different families.

It is putatively thought that HspQ requires a cofactor to form a functional hetero-oligomeric complex.

This enzyme participates in galactose metabolism and ascorbate and aldarate metabolism. It employs one cofactor, calcium.

It employs one cofactor, ADP. At least one compound, NADH is known to inhibit this enzyme.

Tubulin-folding cofactor B is a protein that in humans is encoded by the TBCB gene.

This enzyme participates in urea cycle and metabolism of amino groups. It employs one cofactor, biotin.

Transcription cofactor HES-6 is a protein that in humans is encoded by the HES6 gene.

This enzyme participates in urea cycle and metabolism of amino groups. It employs one cofactor, manganese.

This enzyme participates in monoterpenoid biosynthesis and limonene and pinene degradation. It employs one cofactor, heme.

This enzyme is also called 2-oxo-1,2-dihydroquinoline 8-monooxygenase. It employs one cofactor, iron.

PLCE1 also has a Ca2+ cofactor. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

This enzyme participates in pyruvate metabolism and reductive carboxylate cycle ( fixation). It employs one cofactor, manganese.

Tyrosine hydroxylase catalyzes the reaction in which L-tyrosine is hydroxylated in the meta position to obtain L-3,4-dihydroxyphenylalanine (L-DOPA). The enzyme is an oxygenase which means it uses molecular oxygen to hydroxylate its substrates. One of the oxygen atoms in O2 is used to hydroxylate the tyrosine molecule to obtain L-DOPA and the other one is used to hydroxylate the cofactor. Like the other aromatic amino acid hydroxylases (AAAHs), tyrosine hydroxylase use the cofactor tetrahydrobiopterin (BH4) under normal conditions, although other similar molecules may also work as a cofactor for tyrosine hydroxylase. The AAAHs converts the cofactor 5,6,7,8-tetrahydrobiopterin (BH4) into tetrahydrobiopterin-4a-carbinolamine (4a-BH4).

Tryptophan tryptophylquinone (TTQ) is an enzyme cofactor, generated by posttranslational modification of amino acids within the protein. Methylamine dehydrogenase (MADH), an amine dehydrogenase, requires TTQ for its catalytic function.Davidson VL, Liu A: Uncovering novel biochemistry in the mechanism of tryptophan tryptophylquinone cofactor biosynthesis Curr. Op. Chem. Biol.

This enzyme participates in starch and sucrose metabolism and nucleotide sugars metabolism. It employs one cofactor, NAD+.

After the cofactor TPP decarboxylates pyruvate, the acetyl portion becomes a hydroxyethyl derivative covalently attached to TPP.

Deficiency in any required amino acid or cofactor can impair the synthesis of dopamine, norepinephrine, and epinephrine.

This enzyme participates in alanine and aspartate metabolism and tetracycline biosynthesis. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in urea cycle and metabolism of amino groups. It employs one cofactor, pyridoxal phosphate.

This enzyme is also called 27-hydroxycholesterol 7alpha-hydroxylase. It employs one cofactor, heme- thiolate(P-450).

This enzyme is part of the electron transport system of Ferrobacillus ferrooxidans. It employs one cofactor, iron.

This enzyme participates in c5-branched dibasic acid metabolism and nitrogen metabolism. It employs one cofactor, cobamide.

This enzyme participates in chondroitin sulfate biosynthesis and glycan structures - biosynthesis 1. It employs one cofactor, manganese.

It employs one cofactor, divalent cation. At least one compound, Chelating agent is known to inhibit this enzyme.

Plastocyanin is an electron carrier that transfers the electron from cytochrome b6f to the P700 cofactor of PSI.

Other names in common use include 4-hydroxyphenylacetonitrile monooxygenase, and 4-hydroxyphenylacetonitrile hydroxylase. It employs one cofactor, heme.

DHODH binds to its FMN cofactor in conjunction with ubiquinone to catalyze the oxidation of dihydroorotate to orotate.

It is a starting compound in the synthesis of coenzyme A (CoA), a cofactor for many enzyme processes.

This enzyme participates in glycine, serine and threonine metabolism and cysteine metabolism. It employs one cofactor, pyridoxal phosphate.

Thus, the ristocetin cofactor activity depends only upon high-molecular multimers of the factor present in circulating plasma.

A congenital molybdenum cofactor deficiency disease, seen in infants, is an inability to synthesize molybdenum cofactor, the heterocyclic molecule discussed above that binds molybdenum at the active site in all known human enzymes that use molybdenum. The resulting deficiency results in high levels of sulfite and urate, and neurological damage.

This enzyme participates in glycine, serine and threonine metabolism and vitamin B6 metabolism. It employs one cofactor, pyridoxal phosphate.

All known examples of 4-amino-4-deoxychorismate lyase bind PLP (pyridoxal-5'-phosphate), a cofactor employed during catalysis.

This enzyme participates in benzoate degradation via hydroxylation and toluene and xylene degradation. It employs one cofactor, thiamin diphosphate.

This enzyme participates in phenylalanine, tyrosine and tryptophan biosynthesis and two-component system - general. It employs one cofactor, pyruvate.

Eukaryotes including the fruit fly Drosophila melanogaster and the algae Ostreococcus tauri also use a precursor to this cofactor.

In other cases a coordinated metal cofactor is used in the active site of an enzyme to assist catalysis.

This enzyme is also called isoflavone 3'-monooxygenase. This enzyme participates in isoflavonoid biosynthesis. It employs one cofactor, heme.

Other names in common use include steroid 4,5-dioxygenase, and 3-alkylcatechol 2,3-dioxygenase. It employs one cofactor, iron.

This enzyme is also called AAoxygenase. This enzyme participates in ascorbate and aldarate metabolism. It employs one cofactor, iron.

Na(+)/H(+) exchange regulatory cofactor NHE-RF3 is a protein that in humans is encoded by the PDZK1 gene.

It employs one cofactor, phosphatidylglycerol. Sources of this enzyme includes Micrococcus luteus, Phaseolus aureus, Mycobacterium smegmatis and cotton fibers.

In humans, L-2-hydroxyglutarate dehydrogenase uses FAD as the cofactor, while the E. coli enzyme reduces molecular oxygen.

Jarret Glasscock is a co-founder as well as the Chief Executive Officer of Cofactor Genomics. Cofactor Genomics Contact Glasscock completed his undergraduate degree at the University of Arizona where he majored in Biology with a focus in the Computer Sciences. Upon graduation, Glasscock pursued his doctorate in Genetics at Washington University in St. Louis where he studied under Warren Gish, developer of the NCBI BLAST sequence analysis program.Warren Gish Warren Gish Bio thumb Jon Armstrong, is the Chief Scientific Officer of Cofactor Genomics.

It has also been identified as the enzyme which inserts nickel into sirohydrochlorin in the biosynthesis of cofactor F430, reaction .

The crystal structure of TIPE2 reveals that it contains a large, hydrophobic central cavity that is poised for cofactor binding.

Other names in common use include L-mandelate 4-hydroxylase, and mandelic acid 4-hydroxylase. It employs one cofactor, iron.

This enzyme participates in alanine and aspartate metabolism and glycine, serine and threonine metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme is also called 3-hydroxyphenylacetate 6-monooxygenase. This enzyme participates in styrene degradation. It employs one cofactor, FAD.

This enzyme participates in alanine and aspartate metabolism. It employs one cofactor, FAD. The enzyme is encoded by DDO gene.

Tetrahydrobiopterin is a cofactor for tryptophan hydroxylase (TPH) for the conversion of L-tryptophan (TRP) to 5-hydroxytryptophan (5-HTP).

Typically, a "bumped" ligand/inhibitor analog is designed to bind a corresponding "hole-modified" protein. Bumped ligands are commonly bulkier derivatives of a cofactor of the target protein. Hole-modified proteins are recombinantly expressed with an amino acid substitution from a larger to smaller residue, e.g. glycine or alanine, at the cofactor binding site.

S-Adenosyl- methionine is a cofactor derived from methionine. The methionine-derivative S-adenosyl methionine (SAM) is a cofactor that serves mainly as a methyl donor. SAM is composed of an adenosyl molecule (via 5' carbon) attached to the sulfur of methionine, therefore making it a sulfonium cation (i.e., three substituents and positive charge).

A major mechanism of reversible bioactivation is substrate presentation where an enzyme translocates near its substrate. Another reversible reaction is where a cofactor binds to an enzyme, which then remains active while the cofactor is bound, and stops being active when the cofactor is removed. In protein synthesis, amino acids are carried by transfer RNA (tRNA) molecules and added to a growing polypeptide chain on the ribosome. In order to transfer the amino acids to the ribosome, tRNAs must first be covalently bonded to the amino acid through their 3' CCA terminal.

Unlike many other cofactors, molybdenum cofactor (Moco) cannot be taken up as a nutrient. The cofactor thus requires de novo biosynthesis. Molybdenum cofactor biosynthesis occurs in four steps: (i) the radical-mediated cyclization of nucleotide, guanosine triphosphate (GTP), to (8S)‑3',8‐cyclo‑7,8‑dihydroguanosine 5'‑triphosphate (), (ii) the formation of cyclic pyranopterin monophosphate (cPMP) from the , (iii) the conversion of cPMP into molybdopterin (MPT), (iv) the insertion of molybdate into MPT to form Moco. Two enzyme-mediated reactions convert guanosine triphosphate to the cyclic phosphate of pyranopterin.

Each class of group-transfer reaction is carried out by a particular cofactor, which is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. An example of this are the dehydrogenases that use nicotinamide adenine dinucleotide (NAD+) as a cofactor. Here, hundreds of separate types of enzymes remove electrons from their substrates and reduce NAD+ to NADH. This reduced cofactor is then a substrate for any of the reductases in the cell that require electrons to reduce their substrates.

Cofactor engineering, a subset of metabolic engineering, is defined as the manipulation of the use of cofactors in an organism’s metabolic pathways. In cofactor engineering, the concentrations of cofactors are changed in order to maximize or minimize metabolic fluxes. This type of engineering can be used to optimize the production of a metabolite product or to increase the efficiency of a metabolic network. The use of engineering single celled organisms to create lucrative chemicals from cheap raw materials is growing, and cofactor engineering can play a crucial role in maximizing production.

Cofactor engineering has recently been successful in altering enzymes to prefer NADH as a cofactor instead of NADPH. In 2010, a group of scientists performed cofactor engineering on the enzyme Gre2p, an NADPH-preferring dehydrogenase found in Saccharomyces cerevisiae. Gre2p reduces the compound diketone 2,5-hexanedione into the chiral building blocks (5S)-hydroxy-2-hexanone and (2S,5S)-hexanediol. The scientists determined that Asn9 (Asparagine, position 9) was an important amino acid the active site of Gre2p. Specifically, Asn9 binds to the 3’-hydroxyl group and the 2’-oxygen atom of adenyl ribose moiety.

Since many cofactors are used by different enzymes in multiple pathways, cofactor engineering may be an efficient, cost effective alternative to current methods of metabolic engineering. Yeast are commonly used in the beer and wine industry because they are capable of efficiently producing ethanol through the metabolic pathway fermentation in the absence of oxygen. Fermentation requires the enzyme glycerol-3-phosphate dehydrogenase (GPDH) which depends on the cofactor NADH. This pathway involves the conversion of glucose to both ethanol and glycerol, both of which use NADH as a cofactor.

Molybdenum cofactor biosynthesis protein 1 is a protein that in humans and other animals, fungi, and cellular slime molds, is encoded by the MOCS1 gene. Both copies of this gene are defective in patients with molybdenum cofactor deficiency, type A. Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in molybdopterin biosynthesis. (This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames.

This enzyme is also called 4-hydroxybenzoate 1-monooxygenase. This enzyme participates in 2,4-dichlorobenzoate degradation. It employs one cofactor, FAD.

It creates volatile compounds when mixed with glucose and amino acids in 90 °C. It is a cofactor in tyrosine oxidation.

This enzyme participates in 3 metabolic pathways: cysteine metabolism, selenoamino acid metabolism, and sulfur metabolism. It employs one cofactor, pyridoxal phosphate.

It employs one cofactor, heme. This enzyme needs Ca2+ for activity. White rot fungi secrete this enzyme to aid lignin degradation.

It employs one cofactor, pyridoxal phosphate. Many alliinases contain a novel N-terminal epidermal growth factor-like domain (EGF-like domain).

Glycine decarboxylase is the P-protein of the glycine cleavage system in eukaryotes. The glycine cleavage system catalyzes the degradation of glycine. The P protein binds the alpha- amino group of glycine through its pyridoxal phosphate cofactor. Carbon dioxide is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein.

The systematic name of this enzyme class is dethiobiotin:sulfur sulfurtransferase. This enzyme participates in biotin metabolism. It employs one cofactor, iron-sulfur.

A computational method, IPRO, recently predicted mutations that experimentally switched the cofactor specificity of Candida boidinii xylose reductase from NADPH to NADH.

This enzyme participates in 4 metabolic pathways: fatty acid metabolism, pyruvate metabolism, propanoate metabolism, and butanoate metabolism. It employs one cofactor, PQQ.

Tetrahydrobiopterin was discovered to play a role as an enzymatic cofactor. The first enzyme found to use tetrahydrobiopterin is phenylalanine hydroxylase (PAH).

Similarly, the cofactor retinal forms a Schiff base in rhodopsins, including human rhodopsin (via Lysine 296), which is key in the photoreception mechanism.

This enzyme participates in 3 metabolic pathways: fatty acid metabolism, polyunsaturated fatty acid biosynthesis, and ppar signaling pathway. It employs one cofactor, FAD.

This enzyme is also called 2-halobenzoate 1,2-dioxygenase. This enzyme participates in benzoate degradation via coa ligation. It employs one cofactor, iron.

Parathyroid hormone 1 receptor has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2 and Sodium-hydrogen antiporter 3 regulator 1.

It is involved in the regulation of cell cycle and likely to be a cellular cofactor for HIV-1 accessory gene product Vpr.

This enzyme participates in biosynthesis of steroids. It employs one cofactor, FAD. At least one compound, Dicumarol is known to inhibit this enzyme.

F2RL2 is a cofactor for F2RL3 activation by thrombin. It mediates thrombin- triggered phosphoinositide hydrolysis and is expressed in a variety of tissues.

The pterin cofactor is regenerated by hydration of the carbinolamine product of PAH to quinonoid dihydrobiopterin (qBH2), which is then reduced to BH4.

Similar to copper, iron is both essential as protein cofactor but also dangerous as ferreous iron catalyzes the formation of reactive oxygen species.

Tubulin-specific chaperone A is a protein that in humans is encoded by the TBCA gene. The product of this gene is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state.

"Lipoate" is the conjugate base of lipoic acid, and the most prevalent form of LA under physiological conditions. Most endogenously produced RLA are not "free" because octanoic acid, the precursor to RLA, is bound to the enzyme complexes prior to enzymatic insertion of the sulfur atoms. As a cofactor, RLA is covalently attached by an amide bond to a terminal lysine residue of the enzyme's lipoyl domains. One of the most studied roles of RLA is as a cofactor of the pyruvate dehydrogenase complex (PDC or PDHC), though it is a cofactor in other enzymatic systems as well (described below).

The Moco RNA motif is a conserved RNA structure that is presumed to be a riboswitch that binds molybdenum cofactor or the related tungsten cofactor. Genetic experiments support the hypothesis that the Moco RNA motif corresponds to a genetic control element that responds to changing concentrations of molybdenum or tungsten cofactor. As these cofactors are not available in purified form, in vitro binding assays cannot be performed. However, the genetic data, complex structure of the RNA and the failure to detect a protein involved in the regulation suggest that the Moco RNA motif corresponds to a class of riboswitches.

These tightly bound ions or molecules are usually found in the active site and are involved in catalysis. For example, flavin and heme cofactors are often involved in redox reactions. Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins. An enzyme together with the cofactor(s) required for activity is called a holoenzyme (or haloenzyme).

July 2005 vol. 79 no. 14 8687-8697 First (N-terminal) 180 aminoacids of NS3 has additional role as cofactor domains for NS2 protein.

Only the (R)-(+)-enantiomer (RLA) exists in nature and is essential for aerobic metabolism because RLA is an essential cofactor of many enzyme complexes.

Other names in common use include imidazoleacetic hydroxylase, imidazoleacetate hydroxylase, and imidazoleacetic monooxygenase. This enzyme participates in histidine metabolism. It employs one cofactor, FAD.

This enzyme participates in 5 metabolic pathways: glycolysis / gluconeogenesis, 1,2-dichloroethane degradation, propanoate metabolism, butanoate metabolism, and methane metabolism. It employs one cofactor, PQQ.

This enzyme is also called hydroxyquinol dioxygenase. This enzyme participates in benzoate degradation via hydroxylation and 1,4-dichlorobenzene degradation. It employs one cofactor, iron.

His-1 is held in place over the nickel cofactor in a tight hydrogen bonding network with a glutamic acid residue and an arginine residue.

HCV genome Nonstructural protein 4A (NS4A) is a viral protein found in the hepatitis C virus. It acts as a cofactor for the enzyme NS3.

Grazoprevir blocks NS3, a serine protease enzyme the virus needs for splitting its polyprotein into the functional virus proteins, and NS4A, a cofactor of NS3.

Other names in common use include 2,5-diketocamphane lactonizing enzyme, camphor ketolactonase I, oxygenase, camphor 1,2-mono, and ketolactonase I. It employs one cofactor, iron.

Other names in common use include 4-aminobenzoate hydroxylase, and 4-aminobenzoate monooxygenase. This enzyme participates in 2,4-dichlorobenzoate degradation. It employs one cofactor, FAD.

Other names in common use include 2,4-dichlorophenol hydroxylase, and 2,4-dichlorophenol monooxygenase. This enzyme participates in 1,4-dichlorobenzene degradation. It employs one cofactor, FAD.

Other names in common use include 7,8-dihydroxykynurenate oxygenase, and 7,8-dihydroxykynurenate 8,8alpha-dioxygenase. This enzyme participates in tryptophan metabolism. It employs one cofactor, iron.

Other names in common use include persulfurase, cysteamine oxygenase, and cysteamine:oxygen oxidoreductase. This enzyme participates in taurine and hypotaurine metabolism. It employs one cofactor, iron.

A chromoprotein is a conjugated protein that contains a pigmented prosthetic group (or cofactor). A common example is haemoglobin, which contains a heme cofactor, which is the iron-containing molecule that makes oxygenated blood appear red. Other examples of chromoproteins include other hemochromes, cytochromes, phytochromes and flavoproteins. In hemoglobin there exists a chromoprotein (tetramer MW:4 x 16.125 =64.500), namely heme, consisting of Fe++ four pyrrol rings.

2-Pyridone is not naturally occurring, but a derivative has been isolated as a cofactor in certain hydrogenases.Shima, S.; Lyon, E. J.; Sordel-Klippert, M.; Kauss, M.; Kahnt, J.; Thauer, R. K.; Steinbach, K.; Xie, X.; Verdier, L. and Griesinger, C., "Structure elucidation: The cofactor of the iron-sulfur cluster free hydrogenase Hmd: structure of the light-inactivation product", Angew. Chem. Int. Ed., 2004, 43, 2547-2551.

The generalized reaction is shown below: 504x504px This enzyme is closely related to Lysine 2,3-aminomutase (LAM) and is thought to use similar cofactors and has a similar reaction mechanism. Experimental evidence suggests that glutamate 2,3 aminomutase uses a pyridoxal 5-phosphate cofactor to catalyze the reaction shown. The pyridoxal 5-phosphate cofactor (Vitamin B6) is heavily utilized by enzymes that catalyze aminoacid transformations.

Mechanism of riboflavin kinase. Riboflavin kinase plays an important role in cells, as FMN is an important cofactor. FMN also is a precursor to flavin adenine dinucleotide(FAD), a redox cofactor used by many enzymes, including many in metabolism. In fact, there are some enzymes that are capable of carrying out both the phosphorylation of riboflavin to FMN, as well as the FMN to FAD reaction.

Organic cofactors can be either coenzymes, which are released from the enzyme's active site during the reaction, or prosthetic groups, which are tightly bound to an enzyme. Organic prosthetic groups can be covalently bound (e.g., biotin in enzymes such as pyruvate carboxylase). An example of an enzyme that contains a cofactor is carbonic anhydrase, which uses a zinc cofactor bound as part of its active site.

Biocatalysts are required for the production of chiral building blocks needed in pharmaceuticals and other chemicals used by society. Many such biocatalysts require NADPH as a cofactor. NADPH, a cofactor quite similar to NADH, is both more expensive and less stable than its counterpart NADH. For these reasons, manufacturers would prefer that the biocatalysts they use in their production lines accept NADH over NADPH.

The reaction is catalyzed by the enzyme using a molybdenum cofactor (MoCo), which in the native state consists of a molybdenum (VI) nucleus ligated by two molybdopterin guanine dinucleotide (MGD) ligands and an aspartic acid residue. Two electrons acquired by the cofactor during the reaction, i.e., the hydroxylation of the hydrocarbon, are then transferred via a chain of iron-sulfur clusters connecting the molybdenum with a heme b cofactor in the alpha subunit, from which the electrons are donated to a yet- unknown acceptor. Notably, EBDH exhibits in vitro activity only with artificial electron acceptors of high redox potential, like the ferricenium ion (E0’= +380 mV).

Nickel insertion into a sirohydrochlorin also requires a chelatase as part of the biosynthesis of cofactor F430. Apparently that chelatase is identical to the cobalt chelatase.

Recent computational redesign by Costas Maranas and coworkers was also capable of experimentally switching the cofactor specificity of Candida boidinii xylose reductase from NADPH to NADH.

This evidence coupled with the data that overexpression of oep shows no phenotype corroborates the role of EGF-CFC as an essential cofactor in Nodal signaling.

Other names in common use include isoflavone 2'-monooxygenase (ambiguous), and isoflavone 2'-hydroxylase (ambiguous). This enzyme participates in isoflavonoid biosynthesis. It employs one cofactor, heme.

Other names in common use include 4-nitrophenol hydroxylase, and 4-nitrophenol-2-hydroxylase. This enzyme participates in gamma-hexachlorocyclohexane degradation. It employs one cofactor, FAD.

This enzyme is also called 3-hydroxybenzoate 4-hydroxylase. This enzyme participates in benzoate degradation via hydroxylation and 2,4-dichlorobenzoate degradation. It employs one cofactor, FAD.

Other names in common use include lysine oxygenase, lysine monooxygenase, and L-lysine-2-monooxygenase. This enzyme participates in lysine degradation. It employs one cofactor, FAD.

Actinin alpha 4 has been shown to interact with PDLIM1, Sodium-hydrogen exchange regulatory cofactor 2, Collagen, type XVII, alpha 1, CAMK2A, CAMK2B, MAGI1 and TRIM3.

Other names in common use include anthraniloyl coenzyme A reductase, and 2-aminobenzoyl- CoA monooxygenase/reductase. This enzyme participates in carbazole degradation. It employs one cofactor, FAD.

Other names in common use include oxygenase, gibberellin A44 oxidase, and (gibberellin-44), 2-oxoglutarate:oxygen oxidoreductase. This enzyme participates in diterpenoid biosynthesis. It employs one cofactor, iron.

Other names in common use include cholesterol 7alpha-hydroxylase, and CYP7A1. This enzyme participates in bile acid biosynthesis and ppar signaling pathway. It employs one cofactor, heme.

This enzyme participates in 5 metabolic pathways: alanine and aspartate metabolism, glutamate metabolism, beta-alanine metabolism, propanoate metabolism, and butanoate metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in 5 metabolic pathways: histidine metabolism, tyrosine metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and novobiocin biosynthesis. It employs one cofactor, pyridoxal phosphate.

Other names in common use include 3,9-dihydroxypterocarpan 6a-hydroxylase, and 3,9-dihydroxypterocarpan 6alpha-monooxygenase (erroneous). This enzyme participates in isoflavonoid biosynthesis. It employs one cofactor, heme.

The strength with which a cofactor is bound to an enzyme may vary greatly; non-covalently bound cofactors are typically anchored by hydrogen bonds or electrostatic interactions.

In its oxidized (Ni(III)) state, the coordination geometry of nickel is square pyramidal. The binding of histidine-1 as an axial ligand in the reduced enzyme is uncertain. If histidine is not a ligand in the reduced enzyme, the nickel(II) cofactor would be square planar. However, the His-1 may remain in place throughout the redox cycle, meaning that the nickel cofactor would always have a square-pyramidal geometry.

In addition to its peroxidase activity, it acts as a sensor and a signaling molecule to exogenous H2O2, which activates mitochondrial catalase activity. In eukaryotes, CCP contain a mono-b-type haem cofactor and is targeted to the intermembrane space of the mitochondria. In prokaryotes, CCP contains a c-type dihaem cofactor and is localized to the periplasm of the cell. Both enzymes work to resist peroxide-induced cellular stress.

As a homodimer, sulfite oxidase contains two identical subunits with an N-terminal domain and a C-terminal domain. These two domains are connected by ten amino acids forming a loop. The N-terminal domain has a heme cofactor with three adjacent antiparallel beta sheets and five alpha helices. The C-terminal domain hosts a molybdopterin cofactor that is surrounded by thirteen beta sheets and three alpha helices.

Other names in common use include 2-hydroxyphenylpropionate hydroxylase, melilotate hydroxylase, 2-hydroxyphenylpropionic hydroxylase, and melilotic hydroxylase. This enzyme participates in phenylalanine metabolism. It employs one cofactor, FAD.

Other names in common use include anthranilate 3-hydroxylase, anthranilate hydroxylase, anthranilic hydroxylase, and anthranilic acid hydroxylase. This enzyme participates in tryptophan metabolism. It employs one cofactor, iron.

Dihydrobiopterin (BH2) is a pteridine compound produced in the synthesis of L-DOPA, dopamine, norepinephrine and epinephrine. It is restored to the required cofactor tetrahydrobiopterin by dihydrobiopterin reductase.

This enzyme participates in 4 metabolic pathways: alanine and aspartate metabolism, valine, leucine and isoleucine degradation, beta-alanine metabolism, and propanoate metabolism. It employs one cofactor, pyridoxal phosphate.

This enzyme participates in 3 metabolic pathways: valine, leucine and isoleucine degradation, valine, leucine and isoleucine biosynthesis, and pantothenate and coa biosynthesis. It employs one cofactor, pyridoxal phosphate.

Other names in common use include 3,4-dihydroxyphenylacetic acid 2,3-dioxygenase, HPC dioxygenase, and homoprotocatechuate 2,3-dioxygenase. This enzyme participates in tyrosine metabolism. It employs one cofactor, iron.

Other names in common use include gentisate oxygenase, 2,5-dihydroxybenzoate dioxygenase, gentisate dioxygenase, and gentisic acid oxidase. This enzyme participates in tyrosine metabolism. It employs one cofactor, iron.

It is also incorrectly known as CDP-abequose epimerase, and CDP-D-abequose 2-epimerase. This enzyme participates in starch and sucrose metabolism. It employs one cofactor, NAD+.

The active site of each RPE65 active site contains an Fe(II) cofactor bound by four histidines (His180, His241, His313, and His527), each contributed by a separate blade on the beta- propeller structure. Three of the four histidines are coordinated to nearby glutamic acid residues (Glu148, Glu417, and Glu469), which are thought to help position the histidines to bind the iron cofactor in an octahedral geometry. Phe103, Thr147, and Glu148 surround the active site where they help stabilize the carbocation intermediate and increase the stereoselectivity of RPE65 for 11-cis-retinol over 13-cis-retinol. The RPE65 iron(II) cofactor, showing its coordination with 4 histidine residues and 3 glutamic acid residues.

The enzyme dihydropteroate synthetase is inhibited by sulfonamide antibiotics. Molybdopterin is a cofactor found in virtually all molybdenum and tungsten-containing proteins. Moco biosynthetic pathway in bacteria and humans.

Additional Weibel–Palade body components are the chemokines Interleukin-8 and eotaxin-3, endothelin-1, angiopoietin-2, osteoprotegerin, the P-selectin cofactor CD63/lamp3, and α-1,3-fucosyltransferase VI.

The systematic name of this enzyme class is albendazole,NADPH:oxygen oxidoreductase (sulfoxide-forming). Other names in common use include albendazole oxidase, and albendazole sulfoxidase. It employs one cofactor, FAD.

DNA ligase III along with its cofactor XRCC1 catalyzes the nick-sealing step in short-patch BER in humans. DNA ligase I ligates the break in long-patch BER.

This enzyme participates in tyrosine metabolism. It employs one cofactor, 5-methylene-3,5-dihydroimidazol-4-one (MIO) which is formed autocatalytic rearrangement of the internal tripeptide Ala-Ser-Gly.

Left: protoporphyrin IX. Right: modified form of heme cofactor released from peroxidase by protease digestion under nonreducing conditions. The active site of eosinophil peroxidase contains a single iron atom in tetradentate complexation with a protoporphyrin IX cofactor. It is notable in that this prosthetic group is linked covalently to the polypeptide via ester bonds. Asp232 and Glu380 of EPO are covalently linked through their terminal oxygen atoms to the modified side chains of the protoporphyrin.

Biotin/lipoyl attachment domain has a conserved lysine residue that binds biotin or lipoic acid. Biotin plays a catalytic role in some carboxyl transfer reactions and is covalently attached, via an amide bond, to a lysine residue in enzymes requiring this coenzyme. Lipoamide acyltransferases have an essential cofactor, lipoic acid, which is covalently bound via an amide linkage to a lysine group. The lipoic acid cofactor is found in a variety of proteins.

The name "mycofactocin" is derived from three words, the genus name "Mycobacterium" (across which it is nearly universal), "cofactor" because its presence in a genome predicts the co- occurrence of certain families of enzymes as if it is a cofactor they require, and "bacteriocin" because a radical SAM enzyme critical to its biosynthesis, MftC, is closely related to the key enzyme for the biosynthesis of subtilosin A, a bacteriocin, from its precursor peptide.

The Moco-II RNA motif is a conserved RNA structure identified by bioinformatics. However, only 8 examples of the RNA motif are known. The RNAs are potentially in the 5' untranslated regions of genes related to molybdenum cofactor (Moco), specifically a gene that encodes a molybdenum-binding domain and a nitrate reductase, which uses Moco as a cofactor. Thus the RNA might be involved in the regulation of genes based on Moco levels.

Gephyrin is a protein that in humans is encoded by the GPHN gene. This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperekplexia and also lead to molybdenum cofactor deficiency.

It was discovered by J.G. Hauge as the third redox cofactor after nicotinamide and flavin in bacteria (although he hypothesised that it was naphthoquinone). Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase. In 1979, Salisbury and colleagues as well as Duine and colleagues extracted this prosthetic group from methanol dehydrogenase of methylotrophs and identified its molecular structure. Adachi and colleagues discovered that PQQ was also found in Acetobacter.

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor. This protein is localized to peroxisomes in most eukaryotic cells. Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate, it follows a ping-pong mechanism. Here, its cofactor is oxidised by one molecule of hydrogen peroxide and then regenerated by transferring the bound oxygen to a second molecule of substrate.

Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide syntheses. Chemically, its structure is that of a (dihydropteridine reductase) reduced pteridine derivative (Quinonoid dihydrobiopterin).

Heparin cofactor II (HCII), a protein encoded by the SERPIND1 gene, is a coagulation factor that inhibits IIa, and is a cofactor for heparin and dermatan sulfate ("minor antithrombin"). The product encoded by this gene is a serine proteinase inhibitor which rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. The gene contains five exons and four introns. This protein shares homology with antithrombin and other members of the alpha 1-antitrypsin superfamily.

In the blood, it mainly circulates in a stable noncovalent complex with von Willebrand factor. Upon activation by thrombin (factor IIa), it dissociates from the complex to interact with factor IXa in the coagulation cascade. It is a cofactor to factor IXa in the activation of factor X, which, in turn, with its cofactor factor Va, activates more thrombin. Thrombin cleaves fibrinogen into fibrin which polymerizes and crosslinks (using factor XIII) into a blood clot.

In contrast, 2,3-CTD utilizes Fe2+ as a cofactor to cleave the carbon-carbon bond adjacent to the phenolic hydroxyl groups of catechol, thus yielding 2-hydroxymuconaldehye as its product.

Other names in common use include 4-hydroxyphenylacetate 1-hydroxylase, 4-hydroxyphenylacetic 1-hydroxylase, and 4-HPA 1-hydroxylase. This enzyme participates in tyrosine metabolism.. It employs one cofactor, FAD.

This enzyme participates in 6 metabolic pathways: methionine metabolism, tyrosine metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, novobiocin biosynthesis, and alkaloid biosynthesis i. It employs one cofactor, pyridoxal phosphate.

Other names in common use include polyphosphate glucokinase, polyphosphate-D-(+)-glucose-6-phosphotransferase, and polyphosphate-glucose 6-phosphotransferase. This enzyme participates in glycolysis / gluconeogenesis. It employs one cofactor, neutral salt.

FNR structure with beta barrel domain colored yellow, alpha helix-beta sheet fold colored green, and FAD cofactor colored red. (image from PDB file 3LVB) Plant-type ferredoxin: NADP reductase has two structural domains. The first domain is an antiparallel beta barrel at the amino terminus of the protein that contains the binding domain for the FAD cofactor. The second domain is at the carboxyl terminus of the protein and contains an alpha helix-beta strand fold.

Other cofactors, such as ATP and coenzyme A, were discovered later in the 1900s. The mechanism of cofactor activity was discovered when, Otto Heinrich Warburg determined in 1936 that NAD+ functioned as an electron acceptor. Well after these initial discoveries, scientists began to realize that the manipulation of cofactor concentrations could be used as tools for the improvement of metabolic pathways. An important group of organic cofactors is the family of molecules referred to as vitamins.

UDP-glucose 6-dehydrogenase uses the co-factor NAD+ as the electron acceptor. The transferase UDP-glucuronate pyrophosphorylase removes a UMP and glucuronokinase, with the cofactor ADP, removes the final phosphate leading to -glucuronic acid. The aldehyde group of this compound is reduced to a primary alcohol using the enzyme glucuronate reductase and the cofactor NADPH, yielding -gulonic acid. This is followed by lactone formationutilizing the hydrolase gluconolactonasebetween the carbonyl on C1 and hydroxyl group on C4.

These discoveries led to Krebs being awarded the Nobel Prize in physiology in 1953, which was shared with the German biochemist Fritz Albert Lipmann who also codiscovered the essential cofactor coenzyme A.

2,3-bisphosphoglycerate is required a cofactor for dPGM. In contrast, the iPGM class is independent of 2,3-bisphosphoglycerate and catalyzes the intramolecular transfer of the phosphate group on monophosphoglycerates using a phosphoserineintermediate.

Other names in common use include FAD-dependent malate-vitamin K reductase, malate-vitamin K reductase, and (S)-malate:(quinone) oxidoreductase. This enzyme participates in pyruvate metabolism. It employs one cofactor, FAD.

It employs one cofactor, FAD. The enzyme is commonly localized on the inner surface of the cytoplasmic membrane although another family member (malate dehydrogenase 2 (NAD)) is found in the mitochondrial matrix.

The Gla and EGF-like domains stay connected after the cleavage by a disulfide bond. However, protein S loses its function as an APC cofactor following either this cleavage or binding C4BP.

The Class III enzymes are considered a separate type of enzyme and have a different mechanism of action; these enzymes are NAD+-dependent, whereas HDACs in other classes require Zn2+ as a cofactor.

In molecular biology, the Cys/Met metabolism PLP-dependent enzyme family is a family of proteins including enzymes involved in cysteine and methionine metabolism which use PLP (pyridoxal-5'-phosphate) as a cofactor.

Hydrogen bonds are (red) between protein, water (blue balls) and the cofactor PLP (purple). File:SecondarySSDH.jpg Figure 4 shows the alpha helices (pink) and beta sheets (yellow) involved in the secondary structure of SDH.

Other names in common use include leukotriene-B4 20-hydroxylase, leucotriene-B4 omega-hydroxylase, LTB4 20-hydroxylase, and LTB4 omega-hydroxylase. This enzyme participates in arachidonic acid metabolism. It employs one cofactor, heme.

This enzyme participates in 6 metabolic pathways: lysine degradation, arginine and proline metabolism, phenylalanine metabolism, D-arginine and D-ornithine metabolism, D-alanine metabolism, and peptidoglycan biosynthesis. It employs one cofactor, pyridoxal phosphate.

Other names in common use include 3-hydroxybenzoate 6-hydroxylase, m-hydroxybenzoate 6-hydroxylase, and 3-hydroxybenzoic acid-6-hydroxylase. This enzyme participates in benzoate degradation via hydroxylation. It employs one cofactor, FAD.

Other names in common use include protocatechuate 4,5-oxygenase, protocatechuic 4,5-dioxygenase, and protocatechuic 4,5-oxygenase. This enzyme participates in benzoate degradation via hydroxylation and 2,4-dichlorobenzoate degradation. It employs one cofactor, iron.

This enzyme belongs to the family of oxidoreductases, specifically those acting on diphenols and related substances as donor with oxygen as acceptor. This enzyme participates in ascorbate metabolism. It employs one cofactor, copper.

Other names in common use include 3-hydroxyanthranilate oxygenase, 3-hydroxyanthranilic acid oxygenase, 3-hydroxyanthranilic oxygenase, 3-hydroxyanthranilic acid oxidase and 3HAO. This enzyme participates in tryptophan metabolism. It employs one cofactor, iron.

Sodium-hydrogen exchange regulatory cofactor 2 has been shown to interact with SGK, Actinin alpha 4, Parathyroid hormone receptor 1, Phosphoinositide-dependent kinase-1, EZR, PODXL, Cystic fibrosis transmembrane conductance regulator and PLCB3.

This enzyme participates in 4 metabolic pathways: glycine, serine and threonine metabolism, cysteine metabolism, D-glutamine and D-glutamate metabolism, and D-arginine and D-ornithine metabolism. It employs one cofactor, pyridoxal phosphate.

Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin and the catalytically active metal molybdenum. MoCo is synthesized from cyclic pyranopterin monophosphate (precursor Z) by the heterodimeric enzyme molybdopterin synthase.

Sirtuins that deacetylate histones are structurally and mechanistically distinct from other classes of histone deacetylases (classes I, IIA, IIB and IV), which have a different protein fold and use Zn2+ as a cofactor.

A magnesium cofactor is also required, essential for increasing the electrophilicity of the phosphate on AMP, though this magnesium ion is only held in the active pocket by electrostatic interactions and dissociates easily.

Mammalian transglutaminases among other transglutaminases require Ca2+ ions as a cofactor. Transglutaminases were first described in 1959. The exact biochemical activity of transglutaminases was discovered in blood coagulation protein factor XIII in 1968.

The basic mechanism of heme peroxidases consists in using hydrogen peroxide to produce an activated form of the heme cofactor, in which iron takes the oxidation state +4. The activated oxygen may then be transferred to a substrate in order to convert it into a reactive oxygen species. There are three distinct cycles which EPO can undergo. The first is the halogenation cycle: : [Fe(III)...Por] + H2O2 → [Fe(IV)=O...Por•+] + H2O where Por denotes the heme cofactor, and • denotes a chemical radical.

Factor X, also known by the eponym Stuart–Prower factor, is an enzyme () of the coagulation cascade. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis. Factor X is activated, by hydrolysis, into factor Xa by both factor IX (with its cofactor, factor VIII in a complex known as intrinsic Tenase) and factor VII with its cofactor, tissue factor (a complex known as extrinsic Tenase ).

The active site of the [NiFe]-hydrogenases are described as (NC)2(OC)Fe(μ-SR)2Ni(SR)2 (where SR is cysteinyl). The “FeS-free” hydrogenases have an undetermined active site containing an Fe(CO)2 center. Methanogenesis, the biosynthesis of methane, entails as its final step, the scission of a nickel-methyl bond in cofactor F430. The iron-molybdenum cofactor (FeMoco) of nitrogenases contains an Fe6C unit and is an example of an interstitial carbide found in biology.

Schiff bases have been investigated in relation to a wide range of contexts, including antimicrobial, antiviral and anticancer activity. They have also been considered for the inhibition of amyloid-β aggregation. Schiff bases are common enzymatic intermediates where an amine, such as the terminal group of a lysine residue, reversibly reacts with an aldehyde or ketone of a cofactor or substrate. The common enzyme cofactor PLP forms a Schiff base with a lysine residue and is transaldiminated to the substrate(s).

Full PBG Deaminase Mechanism The first step is believed to involve an E1 elimination of ammonia from porphobilinogen, generating a carbocation intermediate (1). This intermediate is then attacked by the dipyrrole cofactor of porphobilinogen deaminase, which after losing a proton yields a trimer covalently bound to the enzyme (2). This intermediate is then open to further reaction with porphobilinogen (1 and 2 repeated three more times). Once a hexamer is formed, hydrolysis allows hydroxymethylbilane to be released, as well as cofactor regeneration (3).

The mechanism of PEP carboxylase has been well studied. The enzymatic mechanism of forming oxaloacetate is very exothermic and thereby irreversible; the biological Gibbs free energy change (△G°’) is -30kJmol−1. The substrates and cofactor bind in the following order: metal cofactor (either Co2+, Mg2+, or Mn2+), PEP, bicarbonate (HCO3−). The mechanism proceeds in two major steps, as described below and shown in figure 2: Figure 2: the Phosphoenolpyruvate (PEP) carboxylase enzymatic mechanism converting bicarbonate and PEP to oxaloacetate and phosphate.

The hydride ion is accepted by the NAD(P)+ bound to the Rossmann fold. Unique interactions between the cofactor and the Rossmann fold facilitate an isomerization of the enzyme that releases the cofactor while maintaining the integrity of the active site. A water molecule enters the active site and is subsequently activated by a glutamate residue. The activated water then attacks the thioester enzyme-substrate complex in nucleophilic reaction that regenerates the free enzyme, and releases the corresponding carboxylic acid.

Homoserine dehydrogenase has an NAD(P)H cofactor, which then donates a hydrogen to the same carbon, effectively reducing the aldehyde to an alcohol. (Refer to figures 1 and 2). However, the precise mechanism of complete homoserine dehydrogenase catalysis remains unknown. The homoserine dehydrogenase- catalyzed reaction has been postulated to proceed through a bi-bi kinetic mechanism, where the NAD(P)H cofactor binds the enzyme first and is the last to dissociate from the enzyme once the reaction is complete.

The best characterized function of Protein S is its role in the anti coagulation pathway, where it functions as a cofactor to Protein C in the inactivation of Factors Va and VIIIa. Only the free form has cofactor activity. Protein S binds to negatively charged phospholipids via the carboxylated Gla domain. This property allows Protein S to facilitate the removal of cells that are undergoing apoptosis, a form of structured cell death used by the body to remove unwanted or damaged cells.

CD46 complement regulatory protein also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein is a protein which in humans is encoded by the CD46 gene. CD46 is an inhibitory complement receptor.

All three were of the c-terminal EEP-like domain of Nocturnin bound to its cofactor magnesium. In December 2018, the first structure of Nocturnin bound to its natural substrate, NADPH, was determined, 6NF0.

Other names in common use include methyltetrahydroprotoberberine 14-hydroxylase, (S)-cis-N-methyltetrahydroberberine 14-monooxygenase, and (S)-cis-N-methyltetrahydroprotoberberine-14-hydroxylase. This enzyme participates in alkaloid biosynthesis i. It employs one cofactor, heme.

Other names in common use include 2,3-dihydroxy-beta-phenylpropionic dioxygenase, 2,3-dihydroxy-beta-phenylpropionate oxygenase, and 3-(2,3-dihydroxyphenyl)propanoate:oxygen 1,2-oxidoreductase. This enzyme participates in phenylalanine metabolism. It employs one cofactor, iron.

Belongs to the oxidoreductase family, oxidizing metal ions with NADP+ acting as an electron acceptor. Uses FAD as a cofactor when catalyzing the following reaction: 2cob(II)alamin + NADP+ 2aquacob(III)alamin + NADPH + H+.

Therefore, it is unclear whether nadA RNAs are likely to function as cis-regulatory elements or as small RNAs. These is also evidence that this motif acts as a riboswitch for the enzyme cofactor NAD+.

Zinc finger protein ZFPM1 also known as friend of GATA protein 1 or FOG1 is a protein that in humans is encoded by the ZFPM1 gene. It is a cofactor of the GATA1 transcription factor.

Other names in common use include anthranilate hydroxylase, anthranilic hydroxylase, and anthranilic acid hydroxylase. This enzyme participates in 3 metabolic pathways: benzoate degradation via hydroxylation, carbazole degradation, and nitrogen metabolism. It employs one cofactor, iron.

Other names in common use include arginine monooxygenase, arginine decarboxylase, arginine oxygenase (decarboxylating), and arginine decarboxy-oxidase. This enzyme participates in urea cycle and metabolism of amino groups. It has one cofactor: the flavin FAD.

KAT5 also works later in the DNA repair process, as it serves as a cofactor for TRRAP. TRRAP enhances DNA remodeling by binding to chromatin near broken double stranded DNA sequences. KAT5 aids this recognition.

Aspartate transaminase catalyzes the interconversion of aspartate and α-ketoglutarate to oxaloacetate and glutamate. L-Aspartate (Asp) + α-ketoglutarate ↔ oxaloacetate + L-glutamate (Glu) Reaction catalyzed by aspartate aminotransferase As a prototypical transaminase, AST relies on PLP (Vitamin B6) as a cofactor to transfer the amino group from aspartate or glutamate to the corresponding ketoacid. In the process, the cofactor shuttles between PLP and the pyridoxamine phosphate (PMP) form. The amino group transfer catalyzed by this enzyme is crucial in both amino acid degradation and biosynthesis.

Structure of Coenzyme F420 Coenzyme F420 or 8-hydroxy-5-deazaflavin is a coenzyme (sometimes called a cofactor) involved in redox reactions in methanogens, in many Actinobacteria, and sporadically in other bacterial lineages. It is a flavin derivative. The coenzyme is a substrate for coenzyme F420 hydrogenase, 5,10-methylenetetrahydromethanopterin reductase and methylenetetrahydromethanopterin dehydrogenase. A particularly rich natural source of F420 is Mycobacterium smegmatis, in which several dozen enzymes use F420 instead of the related cofactor FMN used by homologous enzymes in most other species.

A network that is present in the cell, but is often unused, may have a desirable product. Instead of engineering a completely new set of pathways to produce the product, cofactor engineering can be applied. By replacing enzymes to use cofactors readily available in a cell, the typically unused network is no longer cofactor-limited, and production may be increased. In addition to modifying the yield of metabolic networks, changing the cofactors used in a network can reduce operation costs when trying to form a desired product.

While the threonine binding site is not perfectly understood, structural studies do reveal how the pyridoxal phosphate cofactor is bound. The PLP cofactor is bonded to a lysine residue by means of a Schiff base, and the phosphate group of PLP is held in place by amine groups derived from a repeating sequence of glycine residues. The aromatic ring is bound to phenylalanine, and the nitrogen on the ring is hydrogen bonded to hydroxyl group-containing residues. Key residues that interact with PLP within the active site.

RDH12 is mainly expressed in neuroretina and is composed of 7 exons encoding a 360-amino acid peptide. Zinc molecules serve as the ligand cofactor with the cofactor NAD. The retinol will interact with the enzyme at the area between those two cofactors. However, not all retinol dehydrogenases in visual cycle are identified, and this remains challenging to scientists due to the overlapping expressions and activity redundancy among two large RDH and RDH-like producing classes: microsomal short-chain dehydrogenase/reductase and cytosolic medium-chain alcohol dehydrogenases.

His group used cryoEM to solve the structure of dynein's cofactor dynactin and the full length dynein complex. They showed how dynein and dynactin come together in the presence of cargos and how this activates transport.

It contains a cofactor binding site for a [4Fe-4S] cluster, a transit peptide, 5 turns, 11 beta strands, and 18 alpha helixes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

High sulfite content in the blood and urine of babies can be caused by molybdenum cofactor deficiency disease which leads to neurological damage and early death unless treated. Treatment, requiring daily injections, became available in 2009.

Other names in common use include steroid 11beta-hydroxylase, steroid 11beta/18-hydroxylase, and oxygenase, steroid 11beta -mono-. This enzyme participates in c21-steroid hormone metabolism and androgen and estrogen metabolism. It employs one cofactor, heme.

Other names in common use include phenol hydroxylase, and phenol o-hydroxylase. This enzyme participates in 3 metabolic pathways: gamma- hexachlorocyclohexane degradation, toluene and xylene degradation, and naphthalene and anthracene degradation. It employs one cofactor, FAD.

Series B, Containing Papers of a Biological Character, Vol. 77, No. 519 (Apr. 12, 1906), pp. 405-420 JSTOR A few years after, Hans von Euler-Chelpin identified the cofactor in the boiled extract as NAD+.

Other names in common use include L-methioninase, methionine lyase, methioninase, methionine dethiomethylase, L-methionine gamma-lyase, and L-methionine methanethiol-lyase (deaminating). This enzyme participates in selenoamino acid metabolism. It employs one cofactor, pyridoxal phosphate.

Therefore, prestin may require an associated cofactor for anion uptake in oocytes; however, this hypothesis is still under question. Experiments have shown that various anions can compete for prestin uptake including malate, chloride, and alkylsulfonic anions.

Diagnosis of molybdenum cofactor deficiency includes early seizures, low blood levels of uric acid, and high levels of sulphite, xanthine, and uric acid in urine. Additionally, the disease produces characteristic MRI images that can aid in diagnosis.

Hypokalemia which is recurrent or resistant to treatment may be amenable to a potassium- sparing diuretic, such as amiloride, triamterene, spironolactone, or eplerenone. Concomitant hypomagnesemia will inhibit potassium replacement, as magnesium is a cofactor for potassium uptake.

Other names in common use include naphthalene dioxygenase, and naphthalene oxygenase. This enzyme participates in 4 metabolic pathways: 1- and 2-methylnaphthalene degradation, naphthalene and anthracene degradation, fluorene degradation, and ethylbenzene degradation. It employs one cofactor, iron.

Interacts with the cofactor or prosthetic group, FAD of flavoproteins and contains a flavin moiety in the form of FAD or FMN (flavin mononucleotide). The domain non-covalently binds oxidized FAD or its reduced form, hydroquinone (FADH2).

Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. Several transcript variants encoding different isoforms have been described for this gene.

The [4Fe-4S]2+cluster is used as a catalytic cofactor, directly coordinating to SAM. Orbital overlap between SAM and a unique Fe atom on the [4Fe-4S]2+cluster has been observed. The predicted role of the [4Fe-4S]2+cofactor is to transfer an electron onto SAM through an inner sphere mechanism, forcing it into an unstable high energy state that ultimately leads to the formation of the 5’deoxyadenosyl radical. The [2Fe-2S]2+cluster is thought to provide a source of sulfur from which to thiolate DTB.

Figure 5. QDO Catalytic Mechanism Dioxygenases that catalyze reactions without the need for a cofactor are much more rare in nature than those that do require them. Two dioxygenases, 1H-3-hydroxy-4-oxo-quinoline 2,4-dioxygenase (QDO) and 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HDO), have been shown to require neither an organic or metal cofactor. These enzymes catalyze the degradation of quinolone heterocycles in a manner similar to quercetin dioxygenase, but are thought to mediate a radical reaction of a dioxygen molecule with a carbanion on the substrate (figure 5).

Phosphoglycerate mutase (PGM) is any enzyme that catalyzes step 8 of glycolysis. They catalyze the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG) through a 2,3-bisphosphoglycerate intermediate. These enzymes are categorized into the two distinct classes of either cofactor-dependent (dPGM) or cofactor- independent (iPGM). The dPGM enzyme () is composed of approximately 250 amino acids and is found in all vertebrates as well as in some invertebrates, fungi, and bacteria.

Structure of 12-oxophytodienoate reductase (OPR3) bound to FMN cofactor, created in Pymol. 12-oxophytodienoate reductase (OPRs) is an enzyme of the family of Old Yellow Enzymes (OYE). OPRs are grouped into two groups: OPRI and OPRII – the second group is the focus of this article, as the function of the first group is unknown, but is the subject of current research. The OPR enzyme utilizes the cofactor flavin mononucleotide (FMN) and catalyzes the following reaction in the jasmonic acid synthesis pathway: Reaction catalyzed by 12-oxophytodienoate reductase in the jasmonic acid synthesis pathway.

The active sites of ALAS utilize three key amino acid side chains: Arg-85 and Thr-430 and Lys-313. Although these three amino acids have been identified to allow this reaction to proceed, they would be inactive without the addition of cofactor pyridoxal 5’-phosphate (PLP) whose role in this synthesis is detailed in the image below. Before the reaction can begin, the PLP cofactor binds to the lysine side chain to form a Schiff base that promotes attack by glycine substrate. Lysine acts as a general base during this mechanism,.

In enzymology, a phosphoglucomutase (glucose-cofactor) () is an enzyme that catalyzes the chemical reaction :alpha-D-glucose 1-phosphate D-glucose 6-phosphate Hence, this enzyme has one substrate, alpha-D-glucose 1-phosphate, and one product, D-glucose 6-phosphate. This enzyme belongs to the family of isomerases, specifically the phosphotransferases (phosphomutases), which transfer phosphate groups within a molecule. The systematic name of this enzyme class is alpha-D-glucose 1,6-phosphomutase (glucose-cofactor). Other names in common use include glucose phosphomutase, and glucose-1-phosphate phosphotransferase.

The active site of the enzyme lies in the interface between the two domains. Like other transaminase enzymes (as well as many enzymes of other classes), BCATs require the cofactor pyridoxal-5'-phosphate(PLP) for activity. PLP has been found to change the conformation of aminotransferase enzymes, locking the conformation of the enzyme via a Schiff base (imine) linkage in a reaction between a lysine residue of the enzyme and the carbonyl group of the cofactor. This conformational change allows the substrates to bind to the active site pocket of the enzymes.

Despite its natural formation, homocysteine has been linked to inflammation, depression, specific forms of dementia, and various types of vascular disease. The remethylation process that detoxifies homocysteine and converts it back to methionine can occur via either of two pathways. The pathway present in virtually all cells involves the enzyme methionine synthase (MS), which requires vitamin B12 as a cofactor, and also depends indirectly on folate and other B vitamins. The second pathway (restricted to liver and kidney in most mammals) involves betaine-homocysteine methyltransferase (BHMT) and requires TMG as a cofactor.

The mechanism of lysyl oxidase occurs via modification of the ε-amino group of a lysine side chain. The enzyme falls into the category of quinone-containing copper amine oxidases, and the reaction is highly dependent on the cofactor lysyl tyrosylquinone (LTQ). The LTQ cofactor is unique among quinones due to its ortho/benzoquinone structure and neutral charge under physiological pH. This can be contrasted with the similar ubiquitous quinocofactor TPQ, which exists as a negatively charged structure under physiological conditions and includes ortho/para-carbonyl resonance functionality.

It is also thought that Asp477 could have important catalytic effects because of its orientation in the middle of the active site and its interactions with the alpha hydroxyl group of the substrate. Glu418, which is located in the deepest region of the active site, plays a critical role in stabilizing the TPP cofactor. To be specific, it is involved in the cofactor-assisted proton abstraction from the substrate molecule. The phosphate group of the substrate also plays an important role in stabilizing the substrate upon its entrance into the active site.

These infants exhibit normal phenylalanine hydroxylase (PAH) enzymatic activity but have a deficiency in dihydropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydrobiopterin (THB or BH4), a cofactor of PAH. Less frequently, DHPR activity is normal but a defect in the biosynthesis of THB exists. In either case, dietary therapy corrects the hyperphenylalaninemia. However, THB is also a cofactor for two other hydroxylation reactions required in the syntheses of neurotransmitters in the brain: the hydroxylation of tryptophan to 5-hydroxytryptophan and of tyrosine to L-dopa.

Pancreatic elastase is a compact globular protein with a hydrophobic core. This enzyme is formed by three subunits. Each subunit binds one calcium ion (cofactor). There are three important metal-binding sites in amino acids 77, 82, 87.

Mouse gene knockout models that block biopterin synthesis completely die shortly after birth due to their inability to produce catecholamines and neurotransmitters. Biopterin synthesis disorders are also a cause of hyperphenylalaninemia; phenylalanine metabolism requires BH4 as a cofactor.

Other names in common use include methylhydroxypyridinecarboxylate oxidase, 2-methyl-3-hydroxypyridine 5-carboxylic acid dioxygenase, methylhydroxypyridine carboxylate dioxygenase, and 3-hydroxy-3-methylpyridinecarboxylate dioxygenase [incorrect]. This enzyme participates in vitamin B6 metabolism. It employs one cofactor, FAD.

The structure of the enzyme was first solved by X-ray crystallography in 1997; and has since been solved several times with various substrates. It is a large alpha- helical protein which binds heme as a redox cofactor.

Other names in common use include lactate oxidative decarboxylase, lactate oxidase, lactic oxygenase, lactate oxygenase, lactic oxidase, L-lactate monooxygenase, lactate monooxygenase, and L-lactate-2-monooxygenase. This enzyme participates in pyruvate metabolism. It employs one cofactor, FMN.

Some are more commonly recognized by name than by number: niacin, pantothenic acid, biotin and folate. Each B vitamin is either a cofactor (generally a coenzyme) for key metabolic processes or is a precursor needed to make one.

Composed of three α-helices and one beta-strand that contribute to the formation of the quaternary structure. This domain contains residues that interact with the active site of the neighboring subunit to facilitate substrate and cofactor binding.

This isoform of 17β-HSD is expressed predominantly in the testis and catalyzes the conversion of androstenedione to testosterone. It preferentially uses NADP as cofactor. Deficiency can result in impaired virilization of genetically male infants, formerly termed male pseudohermaphroditism.

Most of these enzymes contain iron-sulfur (Fe-S) clusters, and a corrinoid cofactor at their active sites. Although the exact mechanism is unknown, research suggests that these two components of the enzyme may be involved in the reduction.

GSH is capable of preventing infection from the influenza virus. Glutathione (GSH) is synthesized in the cytoplasm of liver cells and imported to the mitochondria where it functions as a cofactor for a number of antioxidant and detoxifying enzymes.

The molybdopterin cofactor has a Mo(VI) center, which is bonded to a sulfur from cysteine, an ene-dithiolate from pyranopterin, and two terminal oxygens. It is at this molybdenum center that the catalytic oxidation of sulfite takes place.

It employs sometimes one cofactor, FAD, but in most cases both a heme and a FAD located in separate domains. It makes the enzyme to one of the more complex extracellular oxidoreductases. It is produced by wood degrading organisms.

2010, 298, 634–639.Lindstedt, G.; Lindstedt, S.; Olander, B.; Tofft, M. α-ketoglutarate and hydroxylation of γ-butyrobetaine. Biochim. Biophys. Acta 1968, 158, 503–505.Lindstedt, G.; Lindstedt, S. Cofactor requirements of γ-butyrobetaine hydroxylase from rat liver.

In this respect, pLDH is similar to pGluDH. Nevertheless, the kinetic properties and sensitivities to inhibitors targeted to the cofactor binding site differ significantly and are identifiable by measuring dissociation constants for inhibitors which, differ by up to 21-fold.

Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. This gene, PYGM, encodes a muscle enzyme involved in glycogenolysis. PYGM has a cofactor, pyridoxal 5'-phosphate, that aids this process. PYGM is located in the cytosol, extracellular exosome, and the cytoplasm.

Biopterin synthesis occurs through two principal pathways; the de novo pathway involves three enzymatic steps and proceeds from GTP, while the salvage pathway converts sepiapterin to biopterin. BH4 is the principal active cofactor, and a recycling pathway converts BH2 to BH4.

Kinetic studies show that malate dehydrogenase enzymatic activity is ordered. The cofactor NAD+/NADH is bound to the enzyme before the substrate. The Km value for malate, i.e., the concentration at which the enzyme activity is half-maximal, is 2 mM.

Other names in common use include salicylate hydroxylase, salicylate 1-hydroxylase, salicylate monooxygenase, and salicylate hydroxylase (decarboxylating). This enzyme participates in 3 metabolic pathways: 1- and 2-methylnaphthalene degradation, naphthalene and anthracene degradation, and fluorene degradation. It employs one cofactor, FAD.

Other names in common use include 4-hydroxybenzoate 3-monooxygenase (reduced nicotinamide adenine, dinucleotide (phosphate)), 4-hydroxybenzoate-3-hydroxylase, and 4-hydroxybenzoate 3-hydroxylase. This enzyme participates in benzoate degradation via hydroxylation and 2,4-dichlorobenzoate degradation. It employs one cofactor, FAD.

This enzyme participates in thiamine metabolism. Thiamine pyrophosphate (TPP), a required cofactor for many enzymes in the cell, is synthesised de novo in Salmonella typhimurium. In Saccharomyces cerevisiae, hydroxyethylthiazole kinase expression is regulated at the mRNA level by intracellular thiamin pyrophosphate.

Iodotyrosine deiodinase catalyzes mono- and diiodotyrosine deiodination. The reaction is NADPH-dependent. Flavin mononucleotide (FMN) is a cofactor. Although flavin is commonly utilized in various catalytic reactions, its use in this reductive dehalogenation is unique and not yet fully understood.

In the early steps of the biosynthesis, which starts from glutamic acid, a tetrapyrrole is created by the enzymes deaminase and cosynthetase which transform aminolevulinic acid via porphobilinogen and hydroxymethylbilane to uroporphyrinogen III. The latter is the first macrocyclic intermediate common to haem, sirohaem, cofactor F430, cobalamin and chlorophyll itself. The next intermediates are coproporphyrinogen III and protoporphyrinogen IX, which is oxidised to the fully aromatic protoporphyrin IX. Insertion of iron into protoporphyrin IX in for example mammals gives haem, the oxygen-carrying cofactor in blood, but plants combine magnesium instead to give, after further transformations, chlorophyll for photosynthesis.

Compared to the United States, which has a greater supply of molybdenum in the soil, people living in those areas have about 16 times greater risk for esophageal squamous cell carcinoma. Molybdenum deficiency has also been reported as a consequence of non-molybdenum supplemented total parenteral nutrition (complete intravenous feeding) for long periods of time. It results in high blood levels of sulfite and urate, in much the same way as molybdenum cofactor deficiency. However (presumably since pure molybdenum deficiency from this cause occurs primarily in adults), the neurological consequences are not as marked as in cases of congenital cofactor deficiency.

Prenylated flavin mononucleotide (prFMN) is a cofactor produced by the flavin prenyltransferase UbiX and utilised by UbiD enzymes in their function as reversible decarboxylases. Hence, prFMN is pivotal for catalysis in the ubiquitous microbial UbiDX system. prFMN is flavin prenylated at the N5 and C6 positions resulting in the formation of a fourth non-aromatic ring (Figure 1) prFMN was discovered in 2015 in the University of Manchester by David Leys’ group. upright=2 Two studies in 2015 characterised UbiX as a flavin prenyltransferase, supplying prFMN to UbiD/Fdc1 which utilises the cofactor to catalyse a reversible decarboxylation reaction.

It also shares many structural properties like the shape of the folding lip with catechol-O-methyl transferase (COMT), though it shares less sequence identity. Several features of the structure like this folding lip suggest that PNMT is a recent adaptation to the catecholamine synthesizing enzyme family, evolving later than COMT, but before other methyltransferases like GNMT. S-adenosyl-L-methionine (SAM) is a required cofactor. The active site binding region for the cofactor SAM contains a rich number of pi bonds from phenylalanine and tyrosine residues in the active site help to keep it in its binding pocket through pi stacking.

Lipid-gated ion channels are a class of ion channels whose conductance of ions through the membrane depends directly on lipids. Classically the lipids are membrane resident anionic signaling lipids that bind to the transmembrane domain on the inner leaflet of the plasma membrane with properties of a classic ligand. Other classes of lipid-gated channels include the mechanosensitive ion channels that respond to lipid tension, thickness, and hydrophobic mismatch. A lipid ligand differs from a lipid cofactor in that a ligand derives its function by dissociating from the channel while a cofactor typically derives its function by remaining bound.

The catalytic site forms at the interface between these two domains and interacts with the required cofactor, pyridoxal phosphate, to bind the substrate glycogen. This cofactor is attached by a covalent Schiff base linkage to Lys-680 in the C-terminal domain. At the opposite side of the enzyme, the regulatory face opens up to the cytosol and contains the phosphorylation peptide, which is phosphorylated by phosphorylase kinase and dephosphorylated by the phosphatase PP1, and the AMP site, which is connected to the active site by an adenine loop. Phosphorylation or binding of the allosteric sites induce conformational change that activates the enzyme.

STAMP Alignment of EZH2 (Yellow; PDB: 4MI0) and Human SET7/9 (Cyan; PDB:1O9S) SET Domains with SAM (red) and Lysine (blue) bound. EZH2 is a member of the SET domain family of lysine methyltransferases which function to add methyl groups to lysine side chains of substrate proteins. SET methyltransferases depend on a S-Adenosyl methionine (SAM) cofactor to act as a methyl donor for their catalytic activity. SET domain proteins differ from other SAM-dependent methyltransferases in that they bind their substrate and SAM cofactor on opposite sides of the active site of the enzyme.

As mentioned, irradiation of the co-factor with UV light results in the loss of CO and Fe. In addition the 542 Da compound can be further degraded by a phosphodiesterase (which specifically cleaves phosphate bonds). Hydrolysis of the phosphate bonds generates the ribonucleotide guanine mono-phosphate and a modified 2-pyridone. On the basis of spectroscopic characterization, Shima et al. have proposed a structure for this organic cofactor (minus the iron atom and CO molecules) as shown: Hmd Catalyzed Reaction Although the mechanism by which Hmd acts is unknown, the iron-containing cofactor is in part responsible for the catalytic activity.

Scientists engineered Saccharomyces cerevisiae to overproduce GPDH, which shifted the cells metabolic flux away from ethanol and toward glycerol, by limiting NADH availability in the ethanol production portion of the pathway. The opposite effect was achieved by influencing a separate pathway in the cell, the Glutamate Synthesis pathway. Inactivating the expression of the enzyme glutamate dehydrogenase, which is NADPH dependent, and over expressing the enzymes glutamine synthetase and glutamate synthetase, which rely on NADH as a cofactor shifted the cofactor balance in glutamate synthesis pathway. The pathway is now dependent on NADH rather than NADPH, which decreases NADH availability in the fermentation pathway.

Water oxidation is catalyzed by a manganese-containing cofactor contained in photosystem II known as the oxygen-evolving complex (OEC) or water-splitting complex. Manganese is an important cofactor, and calcium and chloride are also required for the reaction to occur. The stoichiometry this reaction follows: : 2H2O ⟶ 4e− \+ 4H+ \+ O2 The protons are released into the thylakoid lumen, thus contributing to the generation of a proton gradient across the thylakoid membrane. This proton gradient is the driving force for ATP synthesis via photophosphorylation and coupling the absorption of light energy and oxidation of water to the creation of chemical energy during photosynthesis.

Braunstein's best-known work centered on enzymatic transamination and the role of vitamin B6 (specifically, in its pyridoxal phosphate form) as a cofactor in these reactions. Along with Maria Kritzman, Braunstein co-discovered the phenomenon of transamination and described its biological significance in a series of papers beginning in 1937. Later, Braunstein's and Esmond Snell's research groups independently described a general catalytic mechanism for enzymes dependent on the biologically active form of vitamin B6, known as pyridoxal phosphate (PLP), as a cofactor. In his later career, Braunstein focused on X-ray crystallography, attempting to solve the structure of transaminase enzymes.

This method for solving systems of linear equations based on determinants was found in 1684 by Leibniz (Cramer published his findings in 1750). Although Gaussian elimination requires O(n^3) arithmetic operations, linear algebra textbooks still teach cofactor expansion before LU factorization.

Classic PNMT inhibitors include benzimidazoles, quinolones, and purines. Inhibition can also be produced by the addition of S-deoxyadenosyl L-homocysteine, a replacement for the cofactor SAM, which resembles it, but is missing the methyl group, so no methyl transfer is possible.

Methylation is the most common type of alkylation. Methylation in nature is often effected by vitamin B12- and radical-SAM-based enzymes. The SN2-like methyl transfer reaction in DNA methylation. Only the SAM cofactor and cytosine base are shown for simplicity.

Otherwise vanadium is unusual cofactor in biology.Butler, A., "Vanadium haloperoxidases", Current Opinion in Chemical Biology, 1998, 2, 279-285. By virtue of this family of enzymes, a variety of brominated natural products have been isolated from marine sources. Related chloroperoxidase enzymes effect chlorination.

Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease that performs these cuts but it requires the help of another protein (Factor H, CR1, MCP or C4BP) to supply cofactor activity.

Molybdopterin molybdotransferase (, MoeA, Cnx1) is an enzyme with systematic name adenylyl-molybdopterin:molybdate molybdate transferase (AMP-forming). This enzyme catalyses the following chemical reaction : adenylyl-molybdopterin + molybdate \rightleftharpoons molybdenum cofactor + AMP Catalyses the insertion of molybdenum into the ene-dithiol group of molybdopterin.

Other names in common use include kynurenine transaminase (cyclizing), kynurenine 2-oxoglutarate transaminase, kynurenine aminotransferase, and -kynurenine aminotransferase. This enzyme participates in tryptophan metabolism. It employs one cofactor, pyridoxal phosphate. KYAT1, AADAT (aka KYAT2), and KYAT3 are examples of enzymes of this class.

A low level of NADPH, the cofactor required for superoxide synthesis, can lead to CGD. This has been reported in women who are homozygous for the genetic defect causing glucose-6-phosphate dehydrogenase deficiency (G6PD), which is characterised by reduced NADPH levels.

Mutations in the PLOD1 gene have been linked to Kyphoscoliotic Ehlers–Danlos syndrome (kEDS, in the past EDS VI). Mutations in the PLOD2 gene have been linked to Bruck syndrome in humans. A deficiency in its cofactor, vitamin C, is associated with scurvy.

A cyclic enzyme system is a theoretical system of two enzymes sharing a single substrate or cofactor, also referred to as a biochemical switching device. It has been used as a biochemical implementation of a simple computational device, acting as a chemical diode.

Topaquinone (TPQ) is a redox cofactor derived from the amino acid tyrosine. Its name derives from 2,4,5-trihydroxyphenylalanine-quinone. Its structure was first identified in 1990. It is used by copper amine oxidases which contain a tyrosine residue near the active site.

Sirohydrochlorin is a tetrapyrrole macrocyclic metabolic intermediate in the biosynthesis of sirohaem, the iron-containing prosthetic group in sulfite reductase enzymes. It is also the biosynthetic precursor to cofactor F430, an enzyme which catalyzes the release of methane in the final step of methanogenesis.

Chvostek's sign is found in tetany. However, it may also be present in hypomagnesemia. Magnesium is a cofactor for adenylate cyclase, which catalyzes the conversion of ATP to 3',5'-cyclic AMP. The 3',5'-cyclic AMP (cAMP) is required for parathyroid hormone activation.

CesA1 adds ketoisocaproic acid to the adenylation domain. The thiolation domain will then move the ketoisocaproic acid along the ketoreductase domain, which reduces ketoisocaproic acid into D-α-hydroxyisocaproic acid with the cofactor NADPH. In module CesA2, L-alanine is added to the adenylation domain.

Mammals biosynthesize the amino acid cysteine via homocysteine. Cystathionine β-synthase catalyses the condensation of homocysteine and serine to give cystathionine. This reaction uses pyridoxine (vitamin B6) as a cofactor. Cystathionine γ-lyase then converts this double amino acid to cysteine, ammonia, and α-ketobutyrate.

This article concerns a subset of oxides, molecular derivatives. They are also found in several metalloenzymes, e.g. in the molybdenum cofactor and in many iron-containing enzymes. One of the earliest synthetic compounds to incorporate an oxo ligand is sodium ferrate (Na2FeO4) circa 1702.

It has no degrading action on amide, plasminogen and casein. In addition, hementerin inhibits platelet aggregation induced by collagen via the activation of a nitridergic pathway. Inhibition is probably achieved by enhanced nitric oxide synthase activity. Calcium is a cofactor (ligand) in this activity.

Pyrroloquinoline quinone (PQQ), also called methoxatin, is a redox cofactor. It is found in soil and foods such as kiwifruit, as well as human breast milk. Enzymes containing PQQ are called quinoproteins. Glucose dehydrogenase, one of the quinoproteins, is used as a glucose sensor.

Also known as vitamin B12, this form of cobalamin is a required cofactor of methylmalonyl CoA mutase. Even with a functional version of the enzyme at physiologically normal levels, if B12 cannot be converted to this active form, the mutase will be unable to function.

Unexpressed introns are removed by the spliceosome complex in order to create a more concise mRNA transcript. Splicing is just one of many different post- transcriptional modifications that mRNA must undergo before translation. Prp8 has also been hypothesized to be a cofactor in RNA catalysis.

Chemical structure for thiamine pyrophosphate and protein structure of transketolase. Thiamine pyrophosphate cofactor in yellow and xylulose 5-phosphate substrate in black. () Some enzymes do not need additional components to show full activity. Others require non-protein molecules called cofactors to be bound for activity.

The enzymatic activity of the enzyme is lost upon exposure to sunlight or UV. Photolysis causes the release of an iron atom and two molecules of carbon monoxide. In the holoenzyme the Fe and CO molecules are found associated with a 542 Da cofactor.

P protein plays important and multiple roles during transcription and replication of the RNA genome. The multifunctional P protein is encoded by the P gene. P protein acts as a non-catalytic cofactor of large protein polymerase. It is binding to N and L protein.

A 3D representation of the GlmS ribozyme. This is a view of the GlmS ribozyme bound to its catalytic cofactor. A 3D representation of the GlmS ribozyme. This view shows the pre-cleavage state of the Thermoanaerobacter tengcongensis glmS ribozyme bound to glucose-6-phosphate.

Steroidogenesis, including corticosteroid biosynthesis. The corticosteroids are synthesized from cholesterol within the adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase).

The structure of a protein, for example an enzyme, may change upon binding of its natural ligands, for example a cofactor. In this case, the structure of the protein bound to the ligand is known as holo structure, of the unbound protein as apo structure.

The resulting change in protein conformation could lead to phosphorylation of previously inaccessible phosphorylation sites on the C-terminus and the given phosphorylated segment could then liberate the transcription factor HY5 by competing for the same binding site at the negative regulator of photomorphogenesis COP1. A different mechanism may function in Drosophila. The true ground state of the flavin cofactor in Drosophila CRY is still debated, with some models indicating that the FAD is in an oxidized form, while others support a model in which the flavin cofactor exists in anion radical form, •. Recently, researchers have observed that oxidized FAD is readily reduced to • by light.

Photolyase works with its cofactor FADH, flavin adenine dinucleotide, while repairing the DNA. Photolyase is excited by visible light and transfers an electron to the cofactor FADH-. FADH- now in the possession of an extra electron gives the electron to the dimer to break the bond and repair the DNA. This transfer of the electron is done through the tunneling of the electron from the FADH to the dimer. Although the range of the tunneling is much larger than feasible in a vacuum, the tunneling in this scenario is said to be “superexchange-mediated tunneling,” and is possible due to the protein's ability to boost the tunneling rates of the electron.

In addition to evolving individual molecules, Arnold has used directed evolution to co-evolve enzymes in biosynthetic pathways, such as those involved in the production of carotenoids and L-methionine in Escherichia coli (which has the potential to be used as a whole-cell biocatalyst). Arnold has applied these methods to biofuel production. For example, she evolved bacteria to produce the biofuel isobutanol; it can be produced in E. coli bacteria, but the production pathway requires the cofactor NADPH, whereas E. coli makes the cofactor NADH. To circumvent this problem, Arnold evolved the enzymes in the pathway to use NADH instead of NADPH, allowing for the production of isobutanol.

Factor I is a glycoprotein heterodimer consisting of a disulfide linked heavy chain and light chain. The factor I heavy chain has four domains: an FI membrane attack complex (FIMAC) domain, CD5 domain, and low density lipoprotein receptor 1 and 2 (LDLr1 and LDLr2) domains. the heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). Upon binding of the enzyme to the substrate:cofactor complex, the heavy:light chain interface is disrupted, and the enzyme activated by allostery.

Liver cell distribution of N-acetylglutamic acid is highest in the mitochondria at 56% of total N-acetylglutamic acid availability, 24% in the nucleus, and the remaining 20% in the cytosol. Aminoacylase I in liver and kidney cells degrades N-acetylglutamic acid to glutamate and acetate. In contrast, N-acetylglutamic acid is not the allosteric cofactor to carbamyl phosphate synthetase found in the cytoplasm, which is involved in pyrimidine synthesis. N-acetylglutamic acid concentrations increase when protein consumption increases due to the accumulation of ammonia that must be secreted through the urea cycle, which supports the role of N-acetylglutamic acid as the cofactor for CPSI.

In 2016, work published by Dydio et al. reported an artificial metalloenzyme capable of catalyzing intra-/intermolecular carbene C-H insertions into activated/unactivated C-H bonds, with kinetics like that of a native enzyme (Figure 4). The reported catalyst was developed by switching the iron- protoporphyrin cofactor in thermostable P450 enzyme CYP119 with an iridium- methyl-protoporphyrin cofactor (Ir(Me)-PIX), followed by directed evolution. CYP119-Max, a quadruple mutant (C317G, T213G, L69V, V254L), was subsequently obtained. Enantiomeric excesses (ee’s) of up to ±98% were obtained with a fixed catalyst loading of 0.17 mol %. CYP119-Max can also undergo intermolecular insertion reactions, albeit with moderate ee (68%).

The roof of the active site is characterized by conserved base triples, which connect P2.1 and P2.2 stacks and the floor consists of a non-conserved G-U pair, which are splayed apart. By examining superimposition of ribozyme structures in a pre-cleavage state, metabolite bound state and post cleavage state, it was determined there is no gross conformational change upon metabolite binding, which is indicative of a preorganized active site that depends on GlcN6P as a cofactor, not an allosteric activator. The cofactor is bound in a solvent-accessible pocket and the structure suggests that the amine group of GlcN6P is involved in the catalytic process.

The trivial name cofactor F430 was assigned in 1978 based on the properties of a yellow sample extracted from Methanobacterium thermoautotrophicum, which had a spectroscopic maximum at 430 nm. It was identified as the MCR cofactor in 1982 and the complete structure was deduced by X-ray crystallography and NMR spectroscopy. Coenzyme F430 features a reduced porphyrin in a macrocyclic ring system called a corphin. In addition, it possesses two additional rings in comparison to the standard tetrapyrrole (rings A-D), having a γ-lactam ring E and a keto-containing carbocyclic ring F. It is the only natural tetrapyrrole containing nickel, an element rarely found in biological systems.

The remaining opsin, melanopsin, is found in photosensitive ganglion cells and absorbs blue light most strongly. In rhodopsin, the aldehyde group of retinal is covalently linked to the amino group of a lysine residue on the protein in a protonated Schiff base (-NH+=CH-). When rhodopsin absorbs light, its retinal cofactor isomerizes from the 11-cis to the all-trans configuration, and the protein subsequently undergoes a series of relaxations to accommodate the altered shape of the isomerized cofactor. The intermediates formed during this process were first investigated in the laboratory of George Wald, who received the Nobel prize for this research in 1967.

It participates in 3 metabolic pathways: pentose phosphate pathway, methane metabolism, and carbon fixation. It employs one cofactor, thiamin diphosphate. Phosphoketolase was previously used for biotechnological purposes as it enables the construction of synthetic pathways that allow complete carbon conservation without the generation of reducing power.

Bicyclogermacrene synthase (, Ov-TPS4) is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate diphosphate-lyase (bicyclogermacrene-forming). This enzyme catalyses the following chemical reaction : (2E,6E)-farnesyl diphosphate \rightleftharpoons bicyclogermacrene + diphosphate The enzyme from oregano (Origanum vulgare) gives mainly bicyclogermacrene with Mn2+ as a cofactor.

MARs are present in lower eukaryotic microorganisms, have a Rossmannoid-fold and belong to the isochorismatase superfamily. This observation reinforces that the Rossmann structural motifs found in NAD(+)-dependent dehydrogenases can have a dual function working as a nucleotide cofactor binding domain and as a ribonuclease.

Massive volcanism facilitated this process by releasing large amounts of nickel, a scarce metal which is a cofactor for enzymes involved in producing methane. – Lay summary: On the other hand, in the canonical Meishan sections, the nickel concentration increases somewhat after the concentrations have begun to fall.

Unlike many bacterial deazaflavin photolyases that accepts FMN as well as 8-HDF, one such enzyme from the fruit fly only accepts 8-HDF. The FeS-BCP N-terminal domain is homologous to this domain. Instead of an organic cofactor, its chromophore is an iron-sulphur cluster.

Other names in common use include peptidylglycine 2-hydroxylase, peptidyl alpha-amidating enzyme, peptide-alpha-amide synthetase, synthase, peptide alpha-amide, peptide alpha-amidating enzyme, peptide alpha-amide synthase, peptidylglycine alpha-hydroxylase, peptidylglycine alpha-amidating monooxygenase, PAM-A, PAM-B, and PAM. It employs one cofactor, copper.

PLP, the metabolically active form of vitamin B6, is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function, and gene expression. PLP generally serves as a coenzyme (cofactor) for many reactions including decarboxylation, transamination, racemization, elimination, replacement, and beta-group interconversion.

Tetrahydrobiopterin has multiple roles in human biochemistry. The major one is to convert amino acids such as phenylalanine, tyrosine, and tryptophan to precursors of dopamine and serotonin, major monoamine neurotransmitters. It works as a cofactor, being required for an enzyme's activity as a catalyst, mainly hydroxylases.

This enzyme participates in alanine and aspartate metabolism and D-alanine metabolism. It employs one cofactor, pyridoxal phosphate. At least two compounds, 3-Fluoro-D- alanine and D-Cycloserine are known to inhibit this enzyme. The D-alanine produced by alanine racemase is used for peptidoglycan biosynthesis.

Methionine is an essential amino acid required for protein synthesis and one-carbon metabolism. Its synthesis is catalyzed by the enzyme methionine synthase. Methionine synthase eventually becomes inactive due to the oxidation of its cobalamin cofactor. Methionine synthase reductase regenerates a functional methionine synthase via reductive methylation.

Select ITP3K amino acids are shown in blue. Red arrows represent electron pushing. A metal cofactor (Mn2+, magenta) and a highly conserved Asp416 are essential for positioning the ATP beta- and gamma-phosphates. Arg319 (among other amino acids that are not shown) is involved in orienting IP3.

Therefore, it has a predictable antithrombotic response. There is no risk for Heparin Induced Thrombocytopenia/Heparin Induced Thrombosis-Thrombocytopenia Syndrome (HIT/HITTS). It does not require a binding cofactor such as antithrombin and does not activate platelets. These characteristics make bivalirudin an ideal alternative to heparin.

Hence, the hydroxylation of proline is a critical biochemical process for maintaining the connective tissue of higher organisms. Severe diseases such as scurvy can result from defects in this hydroxylation, e.g., mutations in the enzyme prolyl hydroxylase or lack of the necessary ascorbate (vitamin C) cofactor.

Methanophenazine, a phenazine derivative, is a strongly hydrophobic redox- active cofactor with a role in electron transport in some methanogens. This chromophore can be purified from membranes of methanogenic archaea such as Methanosarcina mazei. The enzyme methanosarcina-phenazine hydrogenase (EC 1.12.98.3) has the name methanophenazine hydrogenase as a synonym.

Iron is necessary for photosynthesis and is present as an enzyme cofactor in plants. Iron deficiency can result in interveinal chlorosis and necrosis. Iron is not a structural part of chlorophyll but very much essential for its synthesis. Copper deficiency can be responsible for promoting an iron deficiency.

The kinin-kallikrein system plays a small role in coagulation. Blood clotting cascade. The blood clotting cascade consists of the intrinsic and extrinsic pathway, both of which create thrombin, a protease involved in blood clotting. The intrinsic pathway requires kininogen, specifically high molecular weight kininogen, as a cofactor.

The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis. Mutations in this gene have been shown to be the cause of the spondylo-ocular syndrome. It has also been implicated as cofactor in pseudoxanthoma elasticum.

Cytochrome c with heme c. Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of binding.

It can also be used with highly specific meanings in specialised contexts. In the description of protein structure, in particular in the Protein Data Bank file format, a heteroatom record (HETATM) describes an atom as belonging to a small molecule cofactor rather than being part of a biopolymer chain.

Cyclic pyranopterin monophosphate synthase (, MOCS1A, MoaA, MoaC, molybdenum cofactor biosynthesis protein 1) is an enzyme with systematic name GTP 8,9-lyase (cyclic pyranopterin monophosphate-forming). This enzyme catalyses the following chemical reaction : GTP \rightleftharpoons cyclic pyranopterin monophosphate + diphosphate This enzyme catalyses an early step in the biosynthesis of molybdopterin.

Assembly of the hydrophobic anchor consisting of subunits SDHC and SDHD remains unclear. Especially in case of heme b insertion and even its function. Heme b prosthetic group does not appear to be part of electron transporting pathway within the complex II. The cofactor rather maintains the anchor stability.

Other names in common use include camphor 5-exo-methylene hydroxylase, 2-bornanone 5-exo- hydroxylase, bornanone 5-exo-hydroxylase, camphor 5-exo-hydroxylase, camphor 5-exohydroxylase, camphor hydroxylase, d-camphor monooxygenase, methylene hydroxylase, methylene monooxygenase, D-camphor-exo-hydroxylase, and camphor methylene hydroxylase. It employs one cofactor, heme.

Dopamine beta-hydroxylase (DBH), also known as dopamine beta-monooxygenase, is an enzyme () that in humans is encoded by the DBH gene. Dopamine beta- hydroxylase catalyzes the conversion of dopamine to norepinephrine. Dopamine is converted to norepinephrine by the enzyme dopamine β-hydroxylase. Ascorbic acid serves as a cofactor.

The systematic name of this enzyme class is glycine:2-oxoglutarate aminotransferase. Other names in common use include glutamic-glyoxylic transaminase, glycine aminotransferase, glyoxylate-glutamic transaminase, L-glutamate:glyoxylate aminotransferase, and glyoxylate-glutamate aminotransferase. This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, pyridoxal phosphate.

Succinyl CoA can be formed from methylmalonyl CoA through the utilization of deoxyadenosyl-B12 (deoxyadenosylcobalamin) by the enzyme methylmalonyl-CoA mutase. This reaction, which requires vitamin B12 as a cofactor, is important in the catabolism of some branched-chain amino acids as well as odd-chain fatty acids.

Flavin adenine dinucleotide in its oxidized form, FAD is a cofactor of flavoprotein oxidoreductase enzymes. Flavoprotein pyridine nucleotide cytochrome reductases, including FAD catalyse the interchange of reducing equivalents (H+ or electrons). Initial electron donors and final electron acceptors comprise single electron carriers and two electron carrying nicotinamide dinucleotides respectively.

The crystal structure of the glyoxylate reductase enzyme from the hyperthermophilic archeon Pyrococcus horiskoshii OT3 has been reported. The enzyme exists in the dimeric form. Each monomer has two domains: a substrate- binding domain where glyoxylate binds, and a nucleotide-binding domain where the NAD(P)H cofactor binds.

Representative proteins interacting with the N-domain are Ufd1, Npl4, p47 and FAF1. Examples of cofactors that interact with the carboxy- terminal tail of p97 are PLAA, PNGase, and Ufd2. The molecular basis for cofactor binding has been studied for some cofactors that interact with the p97 N-domain.

In this branch happens the reduction of CO2 to a methyl residue bound to a cofactor. The intermediates are formate for bacteria and formyl-methanofuran for archaea, and also the carriers, tetrahydrofolate and tetrahydropterins respectively in bacteria and archaea, are different, such as the enzymes forming the cofactor-bound methyl group. Otherwise, the carbonyl branch is homologous between the two domains and consists of the reduction of another molecule of CO2 to a carbonyl residue bound to an enzyme, catalyzed by the CO dehydrogenase/acetyl-CoA synthase. This key enzyme is also the catalyst for the formation of acetyl-CoA starting from the products of the previous reactions, the methyl and the carbonyl residues.

Radical SAM enzymes have a conserved cysteine motif, an iron-sulfur cluster within the cysteine motif, as well as S-adenosyl-L-methionine (SAM) as a cofactor. A general radical SAM mechanism involves reducing the iron-sulfur cluster within the enzyme and transferring an electron to the cofactor (SAM), which cleaves a part of the structure and forms a 5'-deoxyadenosyl radical. This 5'-deoxyadenosyl radical will then remove a hydrogen atom from the substrate, forming 5'-deoxyadenosine, and producing a radical on the substrate which will rearrange to form a product. Given that the full mechanism of SPL function is not fully characterized, future studies will likely focus on elucidation of this process.

As a separate option, scientists could increase the flux of B, which may be easier to engineer. This in turn could "tie up" the cofactors needed by A, which would slow enzymatic activity, decreasing output in A. This is one hypothetical example of how cofactor engineering can be used, but there are many other unique cases where scientists use cofactors as a way of altering metabolic pathways. A major advantage to cofactor engineering is that scientists can use it to successfully alter metabolic pathways that are difficult to engineer by means of ordinary metabolic engineering. This is achieved by targeting more easily engineered enzymes in separate pathways, which use the same cofactors.

Crystal structure suggests that FAD is covalently bound to a histidine residue (His99) and further coordinated by hydrogen bonds with number of other amino acid residues within the FAD-binding domain. FAD which is derived from riboflavin (vitamin B2) is thus essential cofactor for SDHA and whole complex II function.

PTEN also refers to a member of the class, phosphatase and tensin homolog. This enzyme class participates in 10 metabolic pathways: inositol phosphate metabolism, phosphatidylinositol signaling system, p53 signaling pathway, focal adhesion, tight junction, endometrial cancer, glioma, prostate cancer, melanoma, and small cell lung cancer. It employs one cofactor, magnesium.

Among the many metabolic processes in which it participates, glutathione is required for the biosynthesis of leukotrienes and prostaglandins. It plays a role in the storage of cysteine. Glutathione enhances the function of citrulline as part of the nitric oxide cycle. It is a cofactor and acts on glutathione peroxidase.

Nitronate monooxygenase (, NMO) is an enzyme with systematic name nitronate:oxygen 2-oxidoreductase (nitrite-forming). This enzyme catalyses the following chemical reaction : ethylnitronate + O2 \rightleftharpoons acetaldehyde + nitrite + other products The enzymes from the fungus Neurospora crassa and the yeast Williopsis saturnus var. mrakii contain non-covalently bound FMN as the cofactor.

In a ring-opening SN2-like mechanism, S2 is displaced as a sulfide or sulfhydryl moiety. Subsequent collapse of the tetrahedral hemithioacetal ejects thiazole, releasing the TPP cofactor and generating a thioacetate on S1 of lipoate. The E1-catalyzed process is the rate-limiting step of the whole pyruvate dehydrogenase complex.

T7 polymerase is extremely promoter-specific and transcribes only DNA downstream of a T7 promoter. The T7 polymerase also requires a double stranded DNA template and Mg2+ ion as cofactor for the synthesis of RNA. It has a very low error rate. T7 polymerase has a molecular weight of 99 kDa.

All subunits of human mitochondrial SDH are encoded in nuclear genome. After translation, SDHA subunit is translocated as apoprotein into the mitochondrial matrix. Subsequently, one of the first steps is covalent binding of the FAD cofactor (flavinylation). This process seems to be regulated by some of the tricarboxylic acid cycle intermediates.

103, no. 30, 2006, pp. 11358-11363. Electron shuttles in the form of redox-active compounds like flavin, which is a cofactor, are also able to transport electrons. These cofactors are secreted by the microbe and reduced by redox participating enzymes such as Cytochrome C embedded on the microbe's cell surface.

The category of EC 2.10 includes enzymes that transfer molybdenum or tungsten-containing groups. However, as of 2011, only one enzyme has been added: molybdopterin molybdotransferase. This enzyme is a component of MoCo biosynthesis in Escherichia coli. The reaction it catalyzes is as follows: adenylyl-molybdopterin + molybdate \rightarrow molybdenum cofactor + AMP.

Acting as a catalyst for reactions, this element is a cofactor for many enzymes, important for sweetness, increasing total soluble solids and boosting vitamin C and juice content for fruit. Iron deficiency is the most common of the micronutrients, causing symptoms of increased prominence of leaf veins and leaves turning white.

This enzyme participates in benzoate degradation via hydroxylation and 2,4-dichlorobenzoate degradation. It employs one cofactor, iron. This enzyme has been found effective at improving organic fluorophore-stability in single-molecule experiments. Commercial preps of the enzyme isolated from Pseudomonas sp generally require further purification to remove strong contaminating nuclease activity.

For example, pyruvate dehydrogenase (PDH) is inhibited when monomethylarsonous acid (MMAIII) targets the thiol group of the lipoic acid cofactor. PDH is a precursor of acetyl-CoA, thus the inhibition of PDH eventually limits the production of ATP in electron transport chain, as well as the production of gluconeogenesis intermediates.

Flavoproteins are ubiquitous biocatalysts binding specific redox active prosthetic groups. The domain is associated with electron transfer proteins and used in electron transport systems. The cofactor flavin-mononucleotide (FMN) is bound non-covalently to the domain, which is functionally interchangeable with iron-sulfur constituted proteins regulating electron transfer or ferredoxins.

Glyoxylate reductase (), first isolated from spinach leaves, is an enzyme that catalyzes the reduction of glyoxylate to glycolate, using the cofactor NADH or NADPH. The systematic name of this enzyme class is glycolate:NAD+ oxidoreductase. Other names in common use include NADH-glyoxylate reductase, glyoxylic acid reductase, and NADH-dependent glyoxylate reductase.

Diagnosis is typically made based on clinical suspicion and a low level of zinc in the blood. Any level below 70 mcg/dl (normal 70-120 mcg/dl)is considered as zinc deficiency. Zinc deficiency could be also associated with low alkaline phosphatase since it acts a cofactor for this enzyme.

This mechanism is supported by findings reported in Widboom et al in 2007.Widboom, P. F., Fielding, E. N., Liu, Y., Bruner, S. D. "Structural basis for cofactor-independent dioxygenation in vancomycin biosynthesis." Nature, 2007, 447, 342-345. Finally, the molecule is transaminated by 4-hydroxyphenylglycine transferase using tyrosine to become DHPG.

Minerals have many roles in the body, which include acting as beneficial antioxidants. Selenium is an essential nutrient, that should be present in trace amounts in the diet. Like other antioxidants, selenium acts as a cofactor to neutralize free radicals. Other minerals act as essential cofactors to biological processes relating to skin health.

High-molecular-weight-kininogen (HK) is a non- enzymatic cofactor involved in the kinin-kallikrein system, which plays a role in blood coagulation, blood pressure regulation, and inflammation. It is synthesized in endothelial cells and is produced mostly by the liver. It is also a precursor protein for bradykinin. Protein structure of bradykinin.

Adenylyltransferase and sulfurtransferase MOCS3 is an enzyme that in humans is encoded by the MOCS3 gene. Molybdenum cofactor (MoCo) is necessary for the function of all molybdoenzymes. One of the enzymes required for the biosynthesis of MoCo is molybdopterin synthase (MPT synthase). The protein encoded by this gene adenylates and activates MPT synthase.

This pathway is also called the “Xylose Reductase-Xylitol Dehydrogenase” or XR-XDH pathway. Xylose reductase (XR) and xylitol dehydrogenase (XDH) are the first two enzymes in this pathway. XR reduces D-xylose to xylitol using NADH or NADPH. Xylitol is then oxidized to D-xylulose by XDH, using the cofactor NAD.

Activated nodal signaling leads to the transcription of the lefty gene. The protein is then expressed, proteolytically cleaved, and finally secreted. Secreted lefty binds to EGF-CFC proteins like one-eyed pinhead in zebrafish keeping the essential cofactor from associating with NODAL/ Activin-like receptor complex. This will effectually block Nodal Signaling.

Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin- dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction : L-tryptophan + tetrahydrobiopterin + O2 \rightleftharpoons 5-Hydroxytryptophan + dihydrobiopterin + H2O It employs one additional cofactor, iron.

Also, studies of mechanism have shown difference in cofactor recruitment between the isoforms. Due to these functional differences, one can see why there is an interest of developing a drug that can selectively target the receptor isoforms. Development of SPRMs has, in some cases, been focused on targeting these two different isoforms.

Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A12 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).

Lipoate–protein ligase (, LplA, lipoate protein ligase, lipoate–protein ligase A, LPL, LPL-B) is an enzyme with systematic name ATP:lipoate adenylyltransferase. This enzyme catalyses the following chemical reaction : (1) ATP + lipoate \rightleftharpoons diphosphate + lipoyl-AMP : (2) lipoyl-AMP + apoprotein \rightleftharpoons protein N6-(lipoyl)lysine + AMP This enzyme requires Mg2+ as a cofactor.

L-gulonolactone oxidase (EC 1.1.3.8) is an enzyme that produces vitamin C, but is non-functional in Haplorrhini (including humans), in some bats, and in guinea pigs. It catalyzes the reaction of L-gulono-1,4-lactone with oxygen to L-xylo-hex-3-gulonolactone and hydrogen peroxide. It uses FAD as a cofactor.

The systematic name of this enzyme class is stearoyl-CoA,ferrocytochrome-b5:oxygen oxidoreductase (9,10-dehydrogenating). Other names in common use include Delta9-desaturase, acyl-CoA desaturase, fatty acid desaturase, and stearoyl- CoA, hydrogen-donor:oxygen oxidoreductase. This enzyme participates in polyunsaturated fatty acid biosynthesis and ppar signaling pathway. It employs one cofactor, iron.

In biochemistry, NAD(P)+ transhydrogenase (Si-specific) () is an enzyme that catalyzes the chemical reaction :NADPH + NAD+ \rightleftharpoons NADP+ \+ NADH Thus, the two substrates of this enzyme are NADPH and NAD+, whereas its two products are NADP+ and NADH. This enzyme participates in nicotinate and nicotinamide metabolism. It employs one cofactor, FAD.

In enzymology, a selenocysteine lyase (SCL) () is an enzyme that catalyzes the chemical reaction :L-selenocysteine + reduced acceptor \rightleftharpoons selenide + L-alanine + acceptor Thus, the two substrates of this enzyme are L-selenocysteine and reduced acceptor, whereas its 3 products are selenide, L-alanine, and acceptor. This enzyme employs one cofactor, pyridoxal phosphate.

Structure of COX-2 inactivated by Aspirin. In the active site of each of the two enzymes, Serine 516 has been acetylated. Also visible is the salicylic acid which has transferred the acyl group, and the heme cofactor. There are at least two different cyclooxygenase isozymes: COX-1 (PTGS1) and COX-2 (PTGS2).

No curative treatment is available for prolidase deficiency at this time, although palliative treatment is possible to some extent. The latter mainly focuses on treating the skin lesions through standard methods and stalling collagen degradation (or boosting prolidase performance, where possible), so as to keep the intracellular dipeptide levels low and give the cells time to resynthesise or absorb what proline they cannot recycle so as to be able to rebuild what collagen does degrade. Patients can be treated orally with ascorbate (a.k.a. vitamin C, a cofactor of prolyl hydroxylase, an enzyme that hydroxylates proline, increasing collagen stability), manganese (a cofactor of prolidase), suppression of collagenase (a collagen degrading enzyme), and local applications of ointments that contain L-glycine and L-proline.

400px A key feature of the cofactor TPP is the relatively acidic proton bound to the carbon atom between the nitrogen and sulfur in the thiazole ring, which has a pKa near 10. This carbon center ionizes to form a carbanion, which adds to the carbonyl group of oxalyl-CoA. This addition is followed by the decarboxylation of oxalyl-CoA, and then the oxidation and removal of formyl-CoA to regenerate the carbanion form of TPP. While the reaction mechanism is shared with other TPP-dependent enzymes, the residues found in the active site of OXC are unique, which has raised questions about whether TDP must be deprotonated by a basic amino acid at a second site away from the carbanion-forming site to activate the cofactor.

The Rossman fold typically binds nucleotide substrates, in this case the UDP-glucuronic acid cofactor involved in glucuronidation by UGT2B7. Generally, the C-terminus of UGT enzymes is highly conserved and binds the UDP-glucuronic acid cofactor, while the N-terminus (not resolved in this structure) is responsible for substrate binding. This first resolved structure indicated that the C-terminus of one of the two dimers projected into the UDP- glucuronic acid binding site of the second dimer, thus rendering the second dimer ineffective. Further studies have investigated dimerization of UGT enzyme polymorphisms and found both homodimer and heterodimer (with genetic polymorphisms of UGT2B7 or other UGT enzymes such as UGT1A1) formation are possible, with some combinations having an effect on enzyme activity.

Secondly, under normal conditions, if Factor V is cleaved by activated protein C instead of thrombin, it can serve as a cofactor for activated protein C. Once bound to Factor V, activated protein C cleaves and inactivates Factor VIIIa. The mutated form of Factor V present in Factor V Leiden, however, serves as a less efficient cofactor of activated protein C. Thus, Factor VIIIa is less efficiently inactivated in Factor V Leiden, further increasing the risk of thrombosis. In fact, Factor V Leiden is the most common cause of inherited thrombosis. Heterozygous Factor V Leiden is present in approximately 5% of the white population in the United States and homozygous Factor V Leiden is found less than 1% of this population.

In enzymology, a retinol dehydrogenase (RDH) () is an enzyme that catalyzes the chemical reaction :retinol + NAD+ \rightleftharpoons retinal + NADH + H+ Sometimes, in addition to or along with NAD+, NADP+ can act as a preferred cofactor in the reaction as well. The substrate of the enzyme can be all- trans- or -cis- retinol. There are at least over 20 different isolated enzymes with RDH activity to date. Thus, the two substrates of this enzyme are retinol and NAD+, whereas its 3 products are retinal, NADH (or NADPH in the case where NADP+ is a cofactor), and H+. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor.

In molecular biology, the group I pyridoxal-dependent decarboxylases, also known as glycine cleavage system P-proteins, are a family of enzymes consisting of glycine cleavage system P-proteins (glycine dehydrogenase (decarboxylating)) from bacterial, mammalian and plant sources. The P protein is part of the glycine decarboxylase multienzyme complex (GDC) also annotated as glycine cleavage system or glycine synthase. The P protein binds the alpha- amino group of glycine through its pyridoxal phosphate cofactor, carbon dioxide is released and the remaining methylamin moiety is then transferred to the lipoamide cofactor of the H protein. GDC consists of four proteins P, H, L and T. Pyridoxal-5'-phosphate-dependent amino acid decarboxylases can be divided into four groups based on amino acid sequence.

Ascorbate has been shown to substitute for the activity of the glutamate residues. (See Figure 3 for mechanism.) Figure 3: Active site of myrosinase during the first step of glucosinolate hydrolysis. Here, ascorbate is used as a cofactor to substitute for the missing second catalytic glutamate in order to cleave the thio-linked glucose.

For \lambda=0,1,\dots, M-1 set s_\lambda=0. Usually M=5 is chosen for polynomials of moderate degrees up to n = 50\. This stage is not necessary from theoretical considerations alone, but is useful in practice. It emphasizes in the H polynomials the cofactor (of the linear factor) of the smallest root.

Factor V (pronounced factor five) is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor. Deficiency leads to predisposition for hemorrhage, while some mutations (most notably factor V Leiden) predispose for thrombosis.

Normal absorption and distribution of copper. Cu = copper, CP = ceruloplasmin, green = ATP7B carrying copper. Copper is needed by the body for a number of functions, predominantly as a cofactor for a number of enzymes such as ceruloplasmin, cytochrome c oxidase, dopamine β-hydroxylase, superoxide dismutase and tyrosinase. Copper enters the body through the digestive tract.

The specificity of a single homeodomain protein is usually not enough to recognize specific target gene promoters, making cofactor binding an important mechanism for controlling binding sequence specificity and target gene expression. To achieve higher target specificity, homeodomain proteins form complexes with other transcription factors to recognize the promoter region of a specific target gene.

The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals in the retina. Two transcript variants encoding different isoforms have been found for this gene.

Their mechanism is poorly understood but may involve a "protein radical". Alkalonic acid (6), a quinone, is the product. Dnr C, alkalonic acid-O-methyltransferase methylates the carboxylic acid end of the molecule forming an ester, using S-adenosyl methionine (SAM) as the cofactor/methyl group donor. The product is alkalonic acid methyl ester (7).

The common biosynthetic precursor for bacteriochlorophylls is chlorophyllide a There are a large number of known bacteriochlorophylls but all have features in common since the biosynthetic pathway involves chlorophyllide a as an intermediate. Isobacteriochlorins, in contrast, are biosynthesised from uroporphyrinogen III in a separate pathway that leads, for example, to siroheme, cofactor F430 and cobalamin.

Intrinsic tenase complex contains the active factor IX (IXa), its cofactor factor VIII (VIIIa), the substrate (factor X), and they are activated by negatively charged surfaces (such as glass, active platelet membrane, sometimes cell membrane of monocytes). These vitamin K-dependent procoagulant factors dock to this surface through their Gla domain with Ca2+ bridges.

The corticosteroids are synthesized from cholesterol within the zona glomerulosa of adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase). Aldosterone and corticosterone share the first part of their biosynthetic pathways.

This enzyme participates in lysine degradation. Iron is a cofactor for gamma-butyrobetaine dioxygenase. Similar to many other 2OG oxygenases, the activity of gamma-butyrobetaine dioxygenase can be stimulated by reducing agents such as ascorbate and glutathione. The catalytic activity of gamma-butyrobetaine dioxygenase can be stimulated with different metal ions, especially potassium ions.

The gene clusters are also homologous, and these subunits are interchangeable to some degree. All nitrogenases use a similar Fe-S core cluster, and the variations come in the cofactor metal. The Anf nitrogenase in Azotobacter vinelandii is organized in an anfHDGKOR operon. This operon still requires some of the Nif genes to function.

GAPDH acts as a reversible metabolic switch under oxidative stress. When cells are exposed to oxidants, they need excessive amounts of the antioxidant cofactor NADPH. In the cytosol, NADPH is reduced from NADP+ by several enzymes, three of them catalyze the first steps of the Pentose phosphate pathway. Oxidant-treatments cause an inactivation of GAPDH.

It inhibits the action the classical and the lectin pathways, more specifically C4. It also has ability to bind C3b. C4BP accelerates decay of C3-convertase and is a cofactor for serine protease factor I which cleaves C4b and C3b. C4BP binds apoptotic and necrotic cells as well as DNA, to clean up after injury.

The protein encoded by this gene is a phosphoprotein that binds to the sodium-hydrogen exchangers (NHEs). This protein serves as an essential cofactor which supports the physiological activity of NHE family members. It has protein sequence similarity to calcineurin B and it is also known to be an endogenous inhibitor of calcineurin activity.

As the monolayer surface area of cord factor increases, so does its toxicity. The length of the carbon chain on cord factor has also shown to affect toxicity; a longer chain shows higher toxicity. Furthermore, fibrinogen has shown to adsorb to monolayers of cord factor and act as a cofactor for its biological effects.

Dihydrosirohydrochlorin is one of several naturally occurring tetrapyrrole macrocyclic metabolic intermediates in the biosynthesis of vitamin B12 (cobalamin). Its oxidised form, sirohydrochlorin, is precursor to sirohaem, the iron-containing prosthetic group in sulfite reductase enzymes. Further biosynthetic transformations convert sirohydrochlorin to cofactor F430 for an enzyme which catalyzes the release of methane in the final step of methanogenesis.

In the reaction that the enzyme uses it requires only one cofactor, a compound required for activation, which is NADP(+) however it is uncertain if this compound truly activates the enzyme. GDP- Fucose is an allosteric inhibitor of the enzyme. Here is a pymol view of the entire structure of the GDP-Mannose 4, 6-Dehydratase enzyme.

A variant of GFP is naturally found in corals, specifically the Anthozoa, and several mutants have been created to span the visible spectra and fluoresce longer and more stably. Other proteins are fluorescent but require a fluorophore cofactor, and hence can only be used in vitro; these are often found in plants and algae (phytofluors, phycobiliprotein such as allophycocyanin).

This gene encodes a member of the highly conserved RCD1 protein family. The encoded protein is a transcriptional cofactor and a core protein of the CCR4-Not deadenylation complex. It may be involved in signal transduction as well as retinoic acid-regulated cell differentiation and development. Alternatively spliced transcript variants have been described for this gene.

Rosenzweig determined structures of important metalloproteins, exerting sustained influence on the field of bioinorganic chemistry. Particular proteins which she determined the structure of are E. coli Mn (II) 2-NrdF and Fe (II) 2-NrdF, which have different coordination sites. This suggests distinct initial binding sites for oxidants during cofactor activation with E. coli and nucleotides.

In order to work as a catalyst, GOx requires a cofactor, flavin adenine dinucleotide (FAD). FAD is a common component in biological oxidation-reduction (redox reactions). Redox reactions involve a gain or loss of electrons from a molecule. In the GOx-catalyzed redox reaction, FAD works as the initial electron acceptor and is reduced to FADH2.

Other names in common use include desulfinase, aminomalonic decarboxylase, aspartate beta-decarboxylase, aspartate omega-decarboxylase, aspartic omega-decarboxylase, aspartic beta- decarboxylase, L-aspartate beta-decarboxylase, cysteine sulfinic desulfinase, L-cysteine sulfinate acid desulfinase, and L-aspartate 4-carboxy-lyase. This enzyme participates in alanine and aspartate metabolism and cysteine metabolism. It employs one cofactor, pyridoxal phosphate.

For more information, see Ediacaran biota. The fossils found that date back to the Precambrian era lack distinct structures since there were no skeletal forms during this period. Skeletons did not arise until the Cambrian Period when oxygen levels increased. This is because skeletons require collagen, which uses Vitamin C as a cofactor, which requires oxygen.

Both reactions are catalyzed by the enzyme glycerol 3-phosphate dehydrogenase with NAD+/NADH as cofactor. DHAP also has a role in the ether-lipid biosynthesis process in the protozoan parasite Leishmania mexicana. DHAP is a precursor to 2-oxopropanal. This conversion is the basis of a potential biotechnological route to the commodity chemical 1,2-propanediol.

Although it is toxic in large doses, selenium is an essential micronutrient for animals. In plants, it sometimes occurs in toxic amounts as forage, e.g. locoweed. Selenium is a component of the amino acids selenocysteine and selenomethionine. In humans, selenium is a trace element nutrient that functions as cofactor for glutathione peroxidases and certain forms of thioredoxin reductase.

Pyridoxine is an indispensable cofactor in the synthesis of the neurotransmitters serotonin, melatonin, dopamine, gama-aminobutyric acid, adrenaline and noradrenaline, and even slight deficiencies can lead to cognitive impairments in humans. Pyridoxine deficiencies have been linked to abnormal sleep and behaviour patterns through downregulation of neurotransmitters and secretion of regulatory hormones in the hypothalamus and pituitary.

The product is aklaviketone (8). Dnr H, aklaviketone reductase, stereospecifically reduces the 17-keto group of the new fourth ring to a 17-OH group to give aklavinone (9). This introduces a new chiral center and NADPH is a cofactor. Dnr F, aklavinone-11-hydroxylase, is a FAD monooxygenase that uses NADPH to activate molecular oxygen for subsequent hydroxylation.

Selenium also plays a role in the functioning of the thyroid gland. It participates as a cofactor for the three thyroid hormone deiodinases. These enzymes activate and then deactivate various thyroid hormones and their metabolites. It may inhibit Hashimotos's disease, an auto-immune disease in which the body's own thyroid cells are attacked by the immune system.

The dihydrolipoate, still bound to a lysine residue of the complex, then migrates to the dihydrolipoyl dehydrogenase (E3) active site where it undergoes a flavin-mediated oxidation, identical in chemistry to disulfide isomerase. First, FAD oxidizes dihydrolipoate back to its lipoate resting state, producing FADH2. Then, a NAD+ cofactor oxidizes FADH2 back to its FAD resting state, producing NADH.

Many proteins require the simultaneous or sequential binding of multiple substrates, cofactors, and/or allosteric effectors. Thermofluor studies of molecules that bind to active site subsites, cofactor sites, or allosteric binding sites can help elucidate specific features of enzyme mechanism that can be important in the design of effective drug screening campaigns and in characterizing novel inhibitory mechanisms.

Methanol, methyl tetrahydrofolate, mono-, di-, and trimethylamine, methanethiol, methyltetrahydromethanopterin, and chloromethane are all methyl donors found in biology as methyl group donors, typically in enzymatic reactions using the cofactor vitamin B12.Ragsdale, S.W. "Catalysis of methyl group transfers involving tetrahydrofolate and B12" Vitamins and Hormones, 2008. These substrates contribute to methyl transfer pathways including methionine biosynthesis, methanogenesis, and acetogenesis.

Carbons 4 and 5 also have a double bond, represented by 'Δ4,5'. The reaction involves a stereospecific and permanent break of the Δ4,5 with the help of NADPH as a cofactor. A hydride anion (H−) is also placed on the α face at the fifth carbon, and a proton on the β face at carbon 4.

This enzyme has 1 substrate, L-serine, and two products, pyruvate and NH3, and uses 1 cofactor, pyridoxal phosphate (PLP). The enzyme's main role is in gluconeogenesis in the liver's cytoplasm. By orienting the substrates and utilizing the PLP coenzyme, SDH lowers the activation energy to convert L-Serine into pyruvate, which can then be converted into glucose.

Moreover, MLEs can facilitate catalysis by attaching the substrate and therefore increasing the nucleophilicity of the carboxylate in order to produce lactone. Muconate lactonizing enzyme actions to catalyze same 1,2 addition-elimination reaction. This can be done with or without a metal cofactor. In the soil microbes, Cis, cis- muconates (Substrate) is converted into muconolactones (product) by MLEs.

Three proteinaceous iron–sulfur reaction centers are found in PSI. Labeled Fx, Fa, and Fb, they serve as electron relays. Fa and Fb are bound to protein subunits of the PSI complex and Fx is tied to the PSI complex. Various experiments have shown some disparity between theories of iron–sulfur cofactor orientation and operation order.

Here, a Rossmann fold domain is inserted at the C-terminal end of the TIM-barrel. Trimethylamine dehydrogenase catalyzes the conversion of trimethylamine to formaldehyde. This reaction requires both a reduced 6-S-cysteinyl Flavin mononucleotide (FMN) cofactor and a reduced iron-sulphur ([4Fe-4S]+) center. FMN is covalently bound within the C-terminal region of the β-barrel.

Nicotinamide adenine dinucleotide (NAD) is a cofactor central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD and NADH respectively.

Therefore, the virus must undergo a E627K mutation in order to perform a mammalian host switch. This region surrounding residue 627 forms a cluster protruding from the enzyme core. With lysine, this PB2 surface region can form a basic patch enabling host cofactor interaction, whereas the glutamic acid residue found in IAVs disrupt this basic region and subsequent interactions.

In enzymology, a 2,5-diaminovalerate transaminase () is an enzyme that catalyzes the chemical reaction :2,5-diaminopentanoate + 2-oxoglutarate \rightleftharpoons 5-amino-2-oxopentanoate + L-glutamate Thus, the two substrates of this enzyme are 2,5-diaminopentanoate and 2-oxoglutarate, whereas its two products are 5-amino-2-oxopentanoate and L-glutamate. It employs one cofactor, pyridoxal phosphate.

A human will typically use up his or her body weight of ATP over the course of the day. Each equivalent of ATP is recycled 1000–1500 times during a single day (). An example of the Rossmann fold, a structural domain of a decarboxylase enzyme from the bacterium Staphylococcus epidermidis () with a bound flavin mononucleotide cofactor.

Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoagulant enzyme.IPR001491 Thrombomodulin Accessed January 19, 2012. Thrombomodulin is also expressed on human mesothelial cell, monocyte and a dendritic cell subset.

NgoMIV) interact with two copies of their recognition sequence but cleave both sequences at the same time. Type IIG restriction endonucleases (e.g., Eco57I) do have a single subunit, like classical Type II restriction enzymes, but require the cofactor AdoMet to be active. Type IIM restriction endonucleases, such as DpnI, are able to recognize and cut methylated DNA.

This enzyme participates in streptomycin biosynthesis and inositol phosphate metabolism. It employs one cofactor, NAD+. The reaction this enzyme catalyses represents the first committed step in the production of all inositol-containing compounds, including phospholipids, either directly or by salvage. The enzyme exists in a cytoplasmic form in a wide range of plants, animals, and fungi.

The Methionine Synthase Reductase (MTRR) gene primarily acts in the reductive regeneration of cob(I)alamin (vitamin B12). Cob(I)alamin is a cofactor that maintains activation of the methionine synthase enzyme (MTR) Methionine synthase, linking folate and methionine metabolism. Donation of methyl groups from folate are utilized for cellular and DNA methylation, influencing epigenetic inheritance.

Phosphoenolpyruvate mutase is thought to exhibit a dissociative mechanism. A magnesium ion is involved as a cofactor. The phosphoryl/phosphate group also appears to interact ionically with Arg159 and His190, stabilizing the reactive intermediate. A phosphoenzyme intermediate is unlikely because the most feasible residues for the covalent adduct can be mutated with only partial loss of function.

Cofactor engineering is significant in the manipulation of metabolic pathways. A metabolic pathway is a series of chemical reactions that occur in an organism. Metabolic engineering is the subject of altering the fluxes within a metabolic pathway. In metabolic engineering, a metabolic pathway can be directly altered by changing the functionality of the enzymes involved in the pathway.

The chemical pulping process requires the manufacturing plant to use a significant amount of energy, as well as many expensive and toxic chemicals. A group of genetic engineers, through cofactor engineering, engineered a genetically superior aspen tree that produced less lignin. These genetically engineered trees have allowed for paper mills to reduce their costs, pollution, and manufacturing time.

It employs one cofactor, magnesium. Delta-cadinene synthase, a sesquiterpene cyclase, is an enzyme expressed in plants that catalyzes a cyclization reaction in terpenoid biosynthesis. The enzyme cyclizes farnesyl diphosphate to delta-cadinene and releases pyrophosphate. Delta-cadinene synthase is one of the key steps in the synthesis of gossypol, a toxic terpenoid produced in cotton seeds.

M. bovis is similar in structure and metabolism to M. tuberculosis. M. bovis is a Gram- positive, acid-fast, rod-shaped, aerobic bacteria. Unlike M. tuberculosis, M. bovis lacks pyruvate kinase activity, due to pykA containing a point mutation that affects binding of Mg2+ cofactor. Pyruvate kinase catalyses the final step of glycolysis, the dephosphorylation of phosphorenolpyruvate to pyruvate.

The glyoxylate reductase enzyme localizes to the cell cytoplasm in plants. It can use both NADPH and NADH as a cofactor, but prefers NADPH. The enzyme substrate, glyoxylate, is a metabolite in plant photorespiration, and is produced in the peroxisome. Glyoxylate is important in the plant cell as it can deactivate RUBISCO and inhibit its activation.

This was proven by inducing a mutation in the SIRVgp19 protein Motif II from the amino acid aspartate to alanine which resulted in a loss of nuclease activity. This protein is functional within pH 7-10. Magnesium chloride was found to be a cofactor to this protein in 1971. Sodium chloride concentrations above 100 mM inhibit SIRV2gp19.

Inorganic substances such as colloidal ferric chloride or molybdenum compounds supposedly acted as cofactors and catalysts. Bahadur also reported having detected ATPase-like and peroxidase-like activity. Bahadur stated that by using molybdenum as a cofactor, the Jeewanu showed capability of reversible photochemical electron transfer, and released a gas mixture of oxygen and hydrogen at a 1:2 ratio.

Mechanisms of metalloproteins often invoke modulation of the second coordination sphere by the protein. For example, an amine cofactor in the second coordination sphere of some hydrogenase enzymes assists in the activation of dihydrogen substrate.J. C. Fontecilla-Camps, A. Volbeda, C. Cavazza, Y. Nicolet "Structure/Function Relationships of [NiFe]- and [FeFe]-Hydrogenases" Chem. Rev. 2007, 107, 4273-4303.

Cycle of NAD(P)H-dependent reduction of FAD to FADH2 by a flavin reductase. The presumed formation of HOCl within the active site of tryptophan 7-halogenase is depicted. Tryptophan 7-halogenases are FADH2-dependent, meaning they require an FADH2 cofactor in order to carry out their reaction. Flavin reductases are responsible for the conversion of FAD to FADH2. For sustained activity in an in vitro setting, tryptophan 7-halogenases thus require either excess FADH2 or the presence of a flavin reductase. Since flavin reductase is itself NAD(P)H-dependent, a recent work studying RebH used a cofactor regeneration system wherein glucose dehydrogenase reduces NAD(P)+ to NAD(P)H, which RebF (RebH's native flavin reductase partner) uses to reduce FAD to FADH2 for subsequent use in RebH’s active site.

Hydroxysteroid 17-beta dehydrogenase 6 is an enzyme that in humans is encoded by the HSD17B6 gene. The protein encoded by this gene has both oxidoreductase and epimerase activities and is involved in androgen catabolism. The oxidoreductase activity can convert 3 alpha-adiol to dihydrotestosterone, while the epimerase activity can convert androsterone to epi-androsterone. Both reactions use NAD+ as the preferred cofactor.

Galactose oxidase (D-galactose:oxygen 6-oxidoreductase, D-galactose oxidase, beta-galactose oxidase; abbreviated GAO, GAOX, GOase; ) is an enzyme that catalyzes the oxidation of D-galactose in some species of fungi. Galactose oxidase belongs to the family of oxidoreductases. Copper ion is required as a cofactor for galactose oxidase. A remarkable feature of galactose oxidase is that it is a free radical enzyme.

In molecular biology, the octopine dehydrogenase family of enzymes act on the CH-NH substrate bond using NAD(+) or NADP(+) as an acceptor. The family includes octopine dehydrogenase , nopaline dehydrogenase , lysopine dehydrogenase and opine dehydrogenase . NADPH is the preferred cofactor, but NADH is also used. Octopine dehydrogenase is involved in the reductive condensation of arginine and pyruvic acid to D-octopine.

They can readily be reused and exhibit improved stability and performance. The methodology is applicable to essentially any enzyme, including cofactor dependent oxidoreductases.Sheldon, R.A.; Sorgedrager, M.J.; Janssen, M.H.A.; Use of cross-linked enzyme aggregates (CLEAs) for performing biotransformations; Chemistry Today, 2007, 25, 62-67. Application to penicillin acylase used in antibiotic synthesis showed large improvements over other type of biocatalysts.

It also seems that in the case of actin, the CAP protein is required as a possible cofactor in actin's final folding states. The exact manner by which this process is regulated is still not fully understood, but it is known that the protein PhLP3 (a protein similar to phosducin) inhibits its activity through the formation of a tertiary complex.

HDC is therefore the primary source of histamine in most mammals and eukaryotes. The enzyme employs a pyridoxal 5'-phosphate (PLP) cofactor, in similarity to many amino acid decarboxylases. Eukaryotes, as well as gram-negative bacteria share a common HDC, while gram-positive bacteria employ an evolutionarily unrelated pyruvoyl-dependent HDC. In humans, histidine decarboxylase is encoded by the HDC gene.

Molybdenum is a cofactor to enzymes important in building amino acids and is involved in nitrogen metabolism. Molybdenum is part of the nitrate reductase enzyme (needed for the reduction of nitrate) and the nitrogenase enzyme (required for biological nitrogen fixation). Reduced productivity as a result of molybdenum deficiency is usually associated with the reduced activity of one or more of these enzymes.

"Hydrobioactive water" is found in all of the Holy Four foods. This, he states, can hydrate a person more than tap water. He also claims there is a, yet undiscovered, cofactor in water which "contains information to help restore your soul and spirit and to support your emotions." He also describes six foods which he considers to be life-challenging.

In enzymology, a phosphoribosyl-ATP diphosphatase () is an enzyme that catalyzes the chemical reaction :1-(5-phosphoribosyl)-ATP + H2O \rightleftharpoons 1-(5-phosphoribosyl)-AMP + diphosphate Thus, the two substrates of this enzyme are 1-(5-phosphoribosyl)-ATP and H2O, whereas its two products are 1-(5-phosphoribosyl)-AMP and diphosphate. This enzyme participates in histidine metabolism. It employs one cofactor, H+.

Gayana Botanica 54(1):1-14. Its growth may be limited by the availability of iron, nickel, zinc, nitrogen and silicon. Cadmium is actually a nutrient for the diatom, and not just a toxin. If zinc is deficient in the environment, the diatom switches to a different version of carbonic anhydrase enzyme, which uses cadmium instead of zinc as a cofactor.

Because the hydroxylase enzymes that perform these reactions require vitamin C as a cofactor, a long-term deficiency in this vitamin results in impaired collagen synthesis and scurvy. These hydroxylation reactions are catalyzed by two different enzymes: prolyl-4-hydroxylase and lysyl-hydroxylase. The reaction consumes one ascorbate molecule per hydroxylation. The synthesis of collagen occurs inside and outside of the cell.

Structure of siroheme Siroheme (or sirohaem) is a heme-like prosthetic group at the active sites of some enzymes to accomplish the six-electron reduction of sulfur and nitrogen. It is a cofactor at the active site of sulfite reductase, which plays a major role in sulfur assimilation pathway, converting sulfite into sulfide, which can be incorporated into the organic compound homocysteine.

Diagram showing orientation and location of different alpha-glucan linkages. α-Glucans (alpha-glucans) are polysaccharides of D-glucose monomers linked with glycosidic bonds of the alpha form. α-Glucans use cofactors in a cofactor site in order to activate a glucan phosphorylase enzyme. This enzyme causes a reaction that transfers a glucosyl portion between orthophosphate and α-I,4-glucan.

6-hydroxypseudooxynicotine dehydrogenase () is an enzyme with systematic name 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one:acceptor 6-oxidoreductase (hydroxylating). This enzyme catalyses the following chemical reaction: : 1-(6-hydroxypyridin-3-yl)-4-(methylamino)butan-1-one + acceptor + H2O \rightleftharpoons 1-(2,6-dihydroxypyridin-3-yl)-4-(methylamino)butan-1-one + reduced acceptor This enzyme contains a cytidylyl molybdenum cofactor.

Aspergillus nuclease S1 is a monomeric protein of a molecular weight of 38 kilodalton. It requires Zn2+ as a cofactor and is relatively stable against denaturing agents like urea, SDS, or formaldehyde. The optimum pH for its activity lies between 4-4.5. Aspergillus nuclease S1 is known to be inhibited somewhat by 50 μM ATP and nearly completely by 1 mM ATP.

All rhodopsins consist of two building blocks, a protein moiety and a reversibly covalently bound non-protein cofactor, retinal (retinaldehyde). The protein structure of rhodopsin consists of a bundle of seven transmembrane helices that form an internal pocket binding the photoreactive chromophore. They form a superfamily with other membrane-bound receptors containing seven transmembrane domains, for example odor and chemokine receptors.

17β-Hydroxysteroid dehydrogenase type 14 also known as 17β-HSD type 14 or 17βHSD14 is an enzyme that in humans is encoded by the HSD17B14 gene. 17βHSD14 catalyzes the stereospecific oxidation and reduction of the 17β carbon atom of androgens and estrogens using NAD(P)(H) as a cofactor. It is primarily expressed in glandular epithelial tissues of breast, ovary, and testis.

This mechanism is dubious due to the long channel separating the flavin cofactor from the tryptophan substrate. Tryptophan 7-halogenase mechanism, depicting the halogenating chloramine intermediate. angstrom. Note the long (>10Å) channel between the chloride ion and tryptophan as well as the intervening Lys79. () Another proposed mechanism involves the interception of flavin hydroperoxide by a halide anion, generating an equivalent of hypohalous acid.

Inactivity of NAGS results in N-acetylglutamate synthase deficiency, a form of hyperammonemia. In many vertebrates, N-acetylglutamate is an essential allosteric cofactor of CPS1, the enzyme that catalyzes the first step of the urea cycle. Without NAG stimulation, CPS1 cannot convert ammonia to carbamoyl phosphate, resulting in toxic ammonia accumulation. Carbamoyl glutamate has shown promise as a possible treatment for NAGS deficiency.

Alpha-bisabolene synthase (, bisabolene synthase) is an enzyme with systematic name (2E,6E)-farnesyl-diphosphate diphosphate-lyase ((E)-alpha-bisabolene- forming). This enzyme catalyses the following chemical reaction : (2E,6E)-farnesyl diphosphate \rightleftharpoons (E)-alpha-bisabolene + diphosphate This synthase requires a divalent cation cofactor (Mg2+ or, to a lesser extent, Mn2+) to neutralize the negative charge of the diphosphate leaving group.

In relation to the second definition, synthetic organic or inorganic catalysts applied to accomplish a chemical transformation accomplished in nature by a biocatalyst (e.g., a purely proteinaceous catalyst, a metal or other cofactor bound to an enzyme, or a ribozyme) can be said to be accomplishing a biomimetic synthesis, where design and characterization of such catalytic systems has been termed biomimetic chemistry.

1993, 71, 39. The concentration of in blood plasma is measured through a test that uses β-hydroxybutyrate dehydrogenase, with NAD+ as an electron-accepting cofactor. The conversion of to acetoacetate, which is catalyzed by this enzyme, reduces the NAD+ to NADH, generating an electrical change; the magnitude of this change can then be used to extrapolate the amount of in the sample.

DAHP is then transformed to 3-dehydroquinate (DHQ), in a reaction catalyzed by DHQ synthase. Although this reaction requires nicotinamide adenine dinucleotide (NAD) as a cofactor, the enzymic mechanism regenerates it, resulting in the net use of no NAD. :quinate catalyzed by 3-dehydroquinate synthase. The mechanism of ring closure is complex, but involves an aldol condensation at C-2 and C-7.

Thermofluor variant specific for flavin- binding proteins. Analogous to thermofluor binding assays, a small volume of protein solution is heated up and the fluorescence increase is followed as function of temperature. In contrast to thermofluor, no external fluorescent dye is needed because the flavin cofactor is already present in the flavin- binding protein and its fluorescence properties change upon unfolding.

In 2009, Monash Children's Hospital at Southern Health in Melbourne, Australia reported that a patient known as Baby Z became the first person to be successfully treated for molybdenum cofactor deficiency type A. The patient was treated with cPMP, a precursor of molybdopterin. Baby Z will require daily injections of cyclic pyranopterin monophosphate (cPMP) for the rest of her life.

In bacteria, a form of pyruvate dehydrogenase (also called pyruvate oxidase, EC 1.2.2.2) exists that links the oxidation of pyruvate into acetate and carbon dioxide to the reduction of ferrocytochrome. In E. coli this enzyme is encoded by the pox B gene and the protein has a flavin cofactor. This enzyme increases the efficiency of growth of E. coli under aerobic conditions.

An enzyme with a deep trefoil knot for the active-site architecture. Acta Crystallogr D 58(Pt 7):1129-37 and proteins,Nureki O, Watanabe K, Fukai S, Ishii R, Endo Y, Hori H, Yokoyama S. (2004). Deep knot structure for construction of active site and cofactor binding site of tRNA modification enzyme. Structure 12(4):593-602 in archaea and in eukaryota.

SET7/9, a representative histone methyltransferase with SAM (red) and peptide undergoing methylation (orange. Rendered from PDB file 4J83.) The SN2-like methyl transfer reaction. Only the SAM cofactor and cytosine base are shown for simplicity. Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features.

Dopamine itself is used as precursor in the synthesis of the neurotransmitters norepinephrine and epinephrine. Dopamine is converted into norepinephrine by the enzyme dopamine β-hydroxylase, with O2 and L-ascorbic acid as cofactors. Norepinephrine is converted into epinephrine by the enzyme phenylethanolamine N-methyltransferase with S-adenosyl-L-methionine as the cofactor. Some of the cofactors also require their own synthesis.

In 2018, the FDA approved an enzyme substitute called pegvaliase which metabolizes phenylalanine. It is for adults who are poorly managed on other treatments. Tetrahydrobiopterin (BH4) (a cofactor for the oxidation of phenylalanine) when taken by mouth can reduce blood levels of this amino acid in some people. Most people, however, with the "classical" sequence of mutations, will have little or no benefit.

In particular, the binding of hexokinase is presumed to play a key role in coupling glycolysis to oxidative phosphorylation. Additionally, VDAC is an important regulator of Ca2+ transport in and out of the mitochondria. Because Ca2+ is a cofactor for metabolic enzymes such as pyruvate dehydrogenase and isocitrate dehydrogenase, energetic production and homeostasis are both affected by VDAC’s permeability to Ca2+.

After molybdopterin is eventually complexed with molybdenum, the complete ligand is usually called molybdenum cofactor. Molybdopterin consists of a pyranopterin, a complex heterocycle featuring a pyran fused to a pterin ring. In addition, the pyran ring features two thiolates, which serve as ligands in molybdo- and tungstoenzymes. In some cases, the alkyl phosphate group is replaced by an alkyl diphosphate nucleotide.

Enzymes that contain the molybdopterin cofactor include xanthine oxidase, DMSO reductase, sulfite oxidase, and nitrate reductase. The only molybdenum-containing enzymes that do not feature molybdopterins are the nitrogenases (enzymes that fix nitrogen). These contain an iron-sulfur center of a very different type, which also usually contains molybdenum. However, if molybdenum is present, it is directly bonded to other metal atoms.

This produces the intermediate 5a,11a-dehydro- oxytetracycline. However, the exact mechanism of this step remains to be unclear. The final step of this biosynthesis occurs through the reduction of a double bond in the α, β - unsaturated ketone of 5a,11a-dehydro- oxytetracycline. In this final step, the cofactor NADPH is employed by TchA (reductase) as the reducing agent.

DNA photolyase, N-terminal is an evolutionary conserved protein domain. This domain binds a light harvesting chromophore that enhanced the spectrum of photolyase or cryptochrome light absorption, i.e. an antenna. It adopts the rossmann fold. The cofactor may be either the pterin 5,10-Methenyltetrahydrofolate (MTHF, ) in folate photolyases () or the deazaflavin 8-hydroxy-7,8-didemethyl-5-deazariboflavin (8-HDF, ) in deazaflavin photolyases ().

12-oxophytodienoate reductase isomers OPR3 (blue) and OPR1 (green) with FMN cofactor (pink). 12-oxophytodienoate reductase has also been shown to practice self-inhibition by dimerization. This is the only flavoprotein known to dimerize for inhibition and this dimerization is thought to be regulated by phosphorylation. The dimerization occurs by the mutual binding of two loops into the two active sites.

The reduction mechanism employed has been shown to be a ping- pong, bi-bi mechanism. The FMN cofactor is first reduced by NADPH, the substrate is then bound, and finally the substrate is reduced by a hydride transfer from NADPH to the substrate’s beta carbon. The Km of OPR3 in Zea mays was found to be 190 micromolar for its substrate OPDA.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is (3S,4R)-3,4-dihydroxycyclohexa-1,5-diene-1,4-dicarboxylate:NAD+ oxidoreductase. Another name in common use is (1R,2S)-dihydroxy-3,5-cyclohexadiene-1,4-dicarboxylate dehydrogenase. This enzyme employs one cofactor, iron.

Other names in common use include microsomal monooxygenase, xenobiotic monooxygenase, aryl-4-monooxygenase, aryl hydrocarbon hydroxylase, microsomal P-450, flavoprotein-linked monooxygenase, and flavoprotein monooxygenase. This enzyme participates in 7 metabolic pathways: fatty acid metabolism, androgen and estrogen metabolism, gamma-hexachlorocyclohexane degradation, tryptophan metabolism, arachidonic acid metabolism, linoleic acid metabolism, and metabolism of xenobiotics by cytochrome p450. It employs one cofactor, heme.

Enzyme changes shape by induced fit upon substrate binding to form enzyme-substrate complex. Hexokinase has a large induced fit motion that closes over the substrates adenosine triphosphate and xylose. Binding sites in blue, substrates in black and Mg2+ cofactor in yellow. (, ) The different mechanisms of substrate binding The classic model for the enzyme-substrate interaction is the induced fit model.

Adenosylcobalamin is needed as cofactor in methylmalonyl-CoA mutase—MUT enzyme. Processing of cholesterol and protein gives propionyl-CoA that is converted to methylmalonyl-CoA, which is used by MUT enzyme to make succinyl- CoA. Vitamin is needed to prevent anemia, since making porphyrin and heme in mitochondria for producing hemoglobin in red blood cells depends on succinyl- CoA made by vitamin .

Heme synthesis in the cytoplasm and mitochondrion The enzymatic process that produces heme is properly called porphyrin synthesis, as all the intermediates are tetrapyrroles that are chemically classified as porphyrins. The process is highly conserved across biology. In humans, this pathway serves almost exclusively to form heme. In bacteria, it also produces more complex substances such as cofactor F430 and cobalamin (vitamin B12).

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme (EC 2.1.1.43) encoded by EZH2 gene, that participates in histone methylation and, ultimately, transcriptional repression. EZH2 catalyzes the addition of methyl groups to histone H3 at lysine 27, by using the cofactor S-adenosyl-L-methionine. Methylation activity of EZH2 facilitates heterochromatin formation thereby silences gene function.

Mutations in the EZH2 gene have been linked with Weaver syndrome, a rare disorder characterized by advanced bone age, macrocephaly, and hypertelorism. The histidine residue in the active site of the wild-type EZH2 was mutated to tyrosine in patients diagnosed with Weaver syndrome. The mutation likely interferes with cofactor binding and causes disruption of the natural function of the protein.

The domains are connected by loops. The monomers connect to each other via interactions between the barrel of one monomer and the sheet of the other. Binding between monomers is relatively weak, and ODC interconverts rapidly between monomeric and dimeric forms in the cell. The pyridoxal phosphate cofactor binds lysine 69 at the C-terminus end of the barrel domain.

Thus, the two substrates of this enzyme are L-glutamate and NAD+, whereas its 4 products are L-glutamine, 2-oxoglutarate, NADH, and H+. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with NAD+ or NADP+ as acceptor. This enzyme participates in glutamate metabolism and nitrogen assimilation. It employs one cofactor, FMN.

In linear algebra, the adjugate or classical adjoint of a square matrix is the transpose of its cofactor matrix. It is also occasionally known as adjunct matrix, though this nomenclature appears to have decreased in usage. The adjugate has sometimes been called the "adjoint", but today the "adjoint" of a matrix normally refers to its corresponding adjoint operator, which is its conjugate transpose.

Jordans' anomaly is a characteristic finding in Chanarin-Dorfman syndrome and other neutral lipid storage diseases. The anomaly is associated with mutations in the PNPLA2 gene, which produces the enzyme adipose triglyceride lipase (ATGL), and the ABHD5 gene, which encodes a cofactor of ATGL. These mutations lead to defective triglyceride breakdown and accumulation of lipid droplets in cells throughout the body.

The MTRR gene is associated with a family of electron transferases known as the Ferredoxin- NADP(+) reductase (FNR) family. Found in 15 primates and over 16 tissues in humans, MTRR is 34 kb long. The gene comprises 15 exons and includes numerous cytolosic mitochondrial mRNA isoforms. Multiple cofactor binding sites assist in the maintenance of MTR activity via reductive remethylation.

For instance Zn2+ is needed to assist the enzyme carbonic anhydrase as it converts carbon dioxide and water to bicarbonate and protons. A widely recognized mineral that acts as a cofactor is iron, which is essential for the proper function of hemoglobin, the oxygen transporting protein found in red blood cells. This example in particular highlights the importance of cofactors in animal metabolism.

Cofactor engineering, offers a distinct approach, and some advantages, to altering a metabolic pathway. Instead of changing the enzymes used in a pathway, the cofactors can be changed. This may give metabolic engineers an advantage due to certain properties of cofactors and how they can be modified. Metabolic pathways can be used by metabolic engineers to create a desired product.

In enzymology, a tetrahydroxypteridine cycloisomerase () is an enzyme that catalyzes the chemical reaction :tetrahydroxypteridine \rightleftharpoons xanthine-8-carboxylate Hence, this enzyme has one substrate, tetrahydroxypteridine, and one product, xanthine-8-carboxylate. This enzyme belongs to the family of isomerases, specifically the class of intramolecular lyases. The systematic name of this enzyme class is tetrahydroxypteridine lyase (isomerizing). It employs one cofactor, NAD+.

RPE65 is a dimer of two symmetrical, enzymatically independent subunits. The active site of each subunit has a seven-bladed beta-propeller structure with four histidines that hold an iron(II) cofactor. This structural motif is common across the studied members of the carotenoid oxygenase family of enzymes. RPE65 is strongly associated with the membrane of the smooth endoplasmic reticulum in RPE cells.

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-3 is an enzyme that in humans is encoded by the PLCB3 gene. The gene codes for the enzyme phospholipase C β3. The enzyme catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals.

There is about 25% similarity between the sequences of AroE and YdiB, but their two structures have similar structures with similar folds. YdiB can utilize NAD or NADP as a cofactor and also reacts with quinic acid. They both have high affinity of their ligands as shown by their similar enzyme (Km) values. Both forms of the enzyme are independently regulated.

Sulcia muelleri is marked down for containing only two genes dedicated to cofactor or vitamin production; these genes code for the synthesis of menaquinone. Sulcia muelleri receives most of its cofactors or vitamins from its cosymbiont. Sulcia muelleri has a minimal set of genes assigned for DNA housekeeping purposes. The only genes it has for DNA repair are the mutL and mutS genes.

Methionine synthase also known as MS, MeSe, MetH is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms part of the S-adenosylmethionine (SAMe) biosynthesis and regeneration cycle. In animals this enzyme requires Vitamin B12 (cobalamin) as a cofactor, whereas the form found in plants is cobalamin-independent.

UbiD activation by UbiX/prFMN was found to be dependent on oxygen suggesting that the reduced prFMN product of UbiX is oxidised to the catalytically relevant form. Several variations of the oxidised prFMN (prFMNox) cofactor were observed: prFMNiminium, hydroxylated prFMNiminium and prFMNketimine. Determination of the prFMN isomer that was catalytically relevant involved incubation of AnFdc1UbiX with phenylpyruvate (of which a small proportion is α-hydroxycinnamic acid which closely resembles cinnamic acid - a model substrate). Incubation with phenylpyruvate lead to an altered UV-Vis spectrum and reversible enzyme inhibition. The crystal structure of AnFdc1UbiX with phenylpyruvate revealed a bond between C1’ of prFMNiminium and a phenylacetaldehyde adduct – a species that can be formed by decarboxylation of α-hydroxycinnamic acid and tautomerisation of the α-hydroxystyrene prFMNiminium adduct. This observation confirmed that it’s the prFMNiminium that is the catalytically relevant cofactor.

The nuclear receptor co-repressor 2 () is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target gene expression. NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT) or T3 receptor-associating cofactor 1 (TRAC-1).

Activated protein C (with protein S as a cofactor) degrades Factor Va and Factor VIIIa. Activated protein C resistance is the inability of protein C to cleave Factor Va and/or Factor VIIIa, which allows for longer duration of thrombin generation and may lead to a hypercoagulable state. This may be hereditary or acquired. The best known and most common hereditary form is Factor V Leiden.

Molybdenum is an essential trace dietary element. Four mammalian Mo-dependent enzymes are known, all of them harboring a pterin-based molybdenum cofactor (Moco) in their active site: sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and mitochondrial amidoxime reductase. People severely deficient in molybdenum have poorly functioning sulfite oxidase and are prone to toxic reactions to sulfites in foods.Blaylock Wellness Report, February 2010, page 3.

The second category of photoredox enabled biocatalytic reactions use an external photocatalyst (PC). Many types of PCs with a large range of redox potentials can be utilized, allowing for greater tunability of reactive compared to using a cofactor. Rose bengal, and external PC, was utilized in tandem with an oxioreductase to enantioselectively deacylate medium sized alpha-acyl-ketones. Using an external PC has some downsides.

Vitamin E is an antioxidant. Vitamin E neutralizes free radicals that accumulate in highly proliferative cells like skin and prevent the deterioration of fibrous tissue caused by these ionized molecules. There are also a couple of water-soluble vitamins that contribute to skin health. Riboflavin (B2) is a cofactor to the metabolism of carbohydrates and when deficient in the diet leads to cracked, brittle skin.

The most widely observed cofactor involved in dioxygenation reactions is iron, but the catalytic scheme employed by these iron-containing enzymes is highly diverse. Iron-containing dioxygenases can be subdivided into three classes on the basis of how iron is incorporated into the active site: those employing a mononuclear iron center, those containing a Rieske [2Fe-2S] cluster, and those utilizing a heme prosthetic group.

Dopamine is the first catecholamine synthesized from DOPA. In turn, norepinephrine and epinephrine are derived from further metabolic modification of dopamine. The enzyme dopamine hydroxylase requires copper as a cofactor (not shown in the diagram) and DOPA decarboxylase requires PLP (not shown in the diagram). The rate limiting step in catecholamine biosynthesis through the predominant metabolic pathway is the hydroxylation of L-tyrosine to L-DOPA.

The low molecular weight of both sulodexide fractions allows for extensive oral absorption compared to unfractionated heparin. The pharmacological effects of sulodexide differ substantially from other glycosaminoglycans and are mainly characterized by a prolonged half-life and reduced effect on global coagulation and bleeding parameters. Due to the presence of both glycosaminoglycan fractions, sulodexide potentiates the antiprotease activities of both antithrombin III and heparin cofactor II simultaneously.

The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein (GlcA-β-1,3-Gal-β-1,3-Gal-β-1,4-Xyl-beta1-O-Ser) linkage found in proteoglycans. Manganese is required as a cofactor. This enzyme differs from the other six beta4GalTs because it lacks the conserved β4GalT1-β4GalT6 Cys residues and it is located in cis-Golgi instead of trans-Golgi.

NDUFV2 is located on the p arm of chromosome 18 in position 11.22 and has 9 exons. The NDUFV2 gene produces a 27.4 kDa protein composed of 249 amino acids. NDUFV2, the protein encoded by this gene, is a member of the complex I 24 kDa subunit family. It contains a cofactor binding site for a 2Fe-2S cluster and a transit peptide domain.

In the biosynthesis of vitamin K, SEPHCHC is involved in the second step of the pathway. The type of reaction is decarboxylating, and to have maximum activity, this enzymes uses the cofactor Mg2+, a magnesium ion. In previous years, it was thought that this reaction led to SHCHC, the product MenH. After further research, we now know that this reaction is a new step in the pathway.

In 1935, Hans Adolf Krebs discovered D-amino acid oxidase after an experiment with porcine kidney homogenates and amino acids. Shortly after, Warburg and Christian observed the oxidase had a FAD cofactor making it the second flavoenzyme to be discovered. In the upcoming years other scientists developed and improved the purification procedure for a porcine D-amino acid oxidase. In 1983, inhibitors for the oxidase were discovered.

Thioredoxin reductase 1, cytoplasmic is an enzyme that in humans is encoded by the TXNRD1 gene. This gene encodes a member of the family of pyridine nucleotide oxidoreductases. This protein reduces thioredoxins as well as other substrates, and plays a role in selenium metabolism and protection against oxidative stress. The functional enzyme is thought to be a homodimer which uses FAD as a cofactor.

The function of eIf1 has some hidden aspects. However, in all eukaryotic cells initiation of mRNA translation starts with scanning via ribosomal 43S preinitiation complexes starting from the 5’ end of the mRNA. Next, induction via eIF1 and eIF1A are needed to disclose the conformation of the 40S subunit in order to induce DEAD-box RNA helicase eIF4A, its cofactor eIF4B, and eIF4G activity.

Zinc transporter ZIP6 is a protein that in humans is encoded by the SLC39A6 gene. Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A6 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003).

The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors.

In addition to a heavy metal chelator, TPEN is also known to be an inducer of apoptosis., thus it may be toxic to cells. One study showed that depletion of zinc by TPEN induced apoptosis in liver cells of rats. This may be because zinc is necessary for normal functioning of the body; for example, zinc acts as a cofactor for enzymes such as insulin-degrading enzyme.

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). Flavoproteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. The flavoproteins are some of the most-studied families of enzymes. Flavoproteins have either FMN or FAD as a prosthetic group or as a cofactor.

In this case, the tungsten-selenium pair has been speculated to function analogously to the molybdenum-sulfur pairing of some molybdenum cofactor- requiring enzymes. Although a tungsten-containing xanthine dehydrogenase from bacteria has been found to contain tungsten-molybdopterin and also non- protein-bound selenium (thus removing the possibility of selenium in selenocysteine or selenomethionine form), a tungsten-selenium molybdopterin complex has not been definitively described.

Arsenic's toxicity comes from the affinity of arsenic(III) oxides for thiols. Thiols, in the form of cysteine residues and cofactors such as lipoic acid and coenzyme A, are situated at the active sites of many important enzymes. Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits lipoic acid, which is a cofactor for pyruvate dehydrogenase.

The active principle was recognized as a special enzyme in the intestine that could activate other enzymes. Pavlov named it enterokinase. The debate of whether enterokinase was a cofactor or enzyme was resolved by Kunitz, who showed that the activation of trypsinogen by enterokinase was catalytic. In the 1950s, cattle trypsinogen was shown to be activated autocatalytically by cleavage of an N-terminal hexapeptide.

Ser-14 is modified by phosphorylase kinase during activation of the enzyme. Lys-680 is involved in binding the pyridoxal phosphate, which is the active form of vitamin B6, a cofactor required by myophosphorylase. By similarity, other sites have been estimated: Tyr-76 binds AMP, Cys-109 and Cys-143 are involved in subunit association, and Tyr-156 may be involved in allosteric control.

All the components of the TRAMP complex are inter-related to each other. For the activity of Poly(A) polymerases likeTrf4p/Trf5p, zinc knuckle proteins are essential. In similar way RNA degradation brought about by exosomes is stimulated by unwinding activity of Ski2 like helicases and Mtr4p which acts as a cofactor. The unwinding activity of Mtr4p is improved by the Trf4p/Air2p in the TRAMP complex.

The three substrates of the enzyme are dopamine, vitamin C (ascorbate), and O2. The products are norepinephrine, dehydroascorbate, and H2O. DBH is a 290 kDa copper-containing oxygenase consisting of four identical subunits, and its activity requires ascorbate as a cofactor. It is the only enzyme involved in the synthesis of small-molecule neurotransmitters that is membrane-bound, making norepinephrine the only known transmitter synthesized inside vesicles.

Irwin C. "Gunny" Gunsalus (June 29, 1912 - October 25, 2008) was an American biochemist who discovered lipoic acid, a vitamin-like substance (an enzyme cofactor) that has been used as a treatment for chronic liver disease, and pyridoxal phosphate, one of the active forms of vitamin B6. In his role as assistant secretary general at the United Nations, he led the international body's research on genetic engineering.

In metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another. The cofactor is, therefore, found in two forms in cells: NAD is an oxidizing agent – it accepts electrons from other molecules and becomes reduced. This reaction forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the main function of NAD.

This reaction is essentially a switch in positions between the carboxylated α-Carbon and the β-Carbon. For this reaction to take place, the enzyme works with a cofactor known as a Vitamin B12, allowing the mechanism to take place through a free radical mechanism. With these three reactions completed to success, the fatty acid is allowed to continue through normal β-Oxidation rounds.

Enzymes often also incorporate non-protein components, such as metal ions or specialized organic molecules known as cofactor (e.g. adenosine triphosphate). Many cofactors are vitamins, and their role as vitamins is directly linked to their use in the catalysis of biological process within metabolism. Catalysis of biochemical reactions in the cell is vital since many but not all metabolically essential reactions have very low rates when uncatalysed.

In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of other fibrous silicates, such as erionite or talc. Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma. This has been confirmed in animal studies, but studies in humans are inconclusive.

In enzymology, a 8-amino-7-oxononanoate synthase () is an enzyme that catalyzes the chemical reaction :6-carboxyhexanoyl-CoA + L-alanine \rightleftharpoons 8-amino-7-oxononanoate + CoA + CO2 Thus, the two substrates of this enzyme are 6-carboxyhexanoyl-CoA and L-alanine, whereas its 3 products are 8-amino-7-oxononanoate, CoA, and CO2. This enzyme participates in biotin metabolism. It employs one cofactor, pyridoxal phosphate.

Lysine 69 on ornithine decarboxylase (ODC) binds the cofactor pyridoxal phosphate to form a Schiff base. Ornithine displaces the lysine to form a Schiff base attached to orthonine, which decarboxylates to form a quinoid intermediate. This intermediate rearranges to form a Schiff base attached to putrescine, which is attacked by lysine to release putrescine product and reform PLP-bound ODC. Hypothesized ornithine decarboxylase mechanism.

Ascorbic acid, the main hydroxyl radical quencher, works as the cofactor providing the hydroxyl radical required to collagen cross-linking; lysine thus becomes hydroxylysine. GA1 worsens during stresses and catabolic episodes, such as fasts and infections. Endogenous catabolism of proteins could be an important route for glutaric acid production. It thus follows that collagen breakdown (and protein breakdown in general) should be prevented by all possible means.

An N-terminal domain contains a 7-stranded parallel β-pleated sheet flanked by α-helices. Paired Rossmann folds within this domain allow GALE to tightly bind one NAD+ cofactor per subunit. A 6-stranded β-sheet and 5 α-helices comprise GALE's C-terminal domain. C-terminal residues bind UDP, such that the subunit is responsible for correctly positioning UDP-glucose or UDP-galactose for catalysis.

In enzymology, a methionine racemase () is an enzyme that catalyzes the chemical reaction :L-methionine \rightleftharpoons D-methionine Hence, this enzyme has one substrate, L-methionine, and one product, D-methionine. This enzyme belongs to the family of isomerases, specifically those racemases and epimerases acting on amino acids and derivatives. The systematic name of this enzyme class is methionine racemase. It employs one cofactor, pyridoxal phosphate.

The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene.

The enzyme is made up of 389-441 amino acids and forms four identical subunits. The active molecule is composed of two tightly associated dimers, the interface at which lies the active site. Each of the dimers has a pyridoxal 5’-phosphate (PLP) cofactor. Six amino acids located near the active site are involved in the reaction, namely Tyr59, Arg61, Tyr114, Cys116, Lys240, and Asp241.

Besides the selenocysteine-containing selenoproteins, there are also some selenoproteins known from bacterial species, which have selenium bound noncovalently. Most of these proteins are thought to contain a selenide-ligand to a molybdopterin cofactor at their active sites (e.g. nicotinate dehydrogenase of Eubacterium barkeri, or xanthine dehydrogenases). Selenium is also specifically incorporated into modified bases of some tRNAs (as 2-seleno-5-methylaminomethyl-uridine).

People with high levels of factor VIII are at increased risk for deep vein thrombosis and pulmonary embolism. Copper is a required cofactor for factor VIII and copper deficiency is known to increase the activity of factor VIII. There is a formulation as a medication that is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.

The systematic name of this enzyme class is S-adenosyl-L-methionine methylthioadenosine-lyase(1-aminocyclopropane-1-carboxylate-forming). Other names in common use include 1-aminocyclopropanecarboxylate synthase, 1-aminocyclopropane-1-carboxylic acid synthase, 1-aminocyclopropane-1-carboxylate synthetase, aminocyclopropanecarboxylic acid synthase, aminocyclopropanecarboxylate synthase, ACC synthase, and S-adenosyl- L-methionine methylthioadenosine-lyase. This enzyme participates in propanoate metabolism. It employs one cofactor, pyridoxal phosphate.

The gene codes for the enzyme phospholipase C β2. The enzyme catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11, as well as G-beta gamma subunits.

The aromatic ring in PLP is fixed in place by an almost coplanar tyrosine residue. It is believed that this configuration increases the electron sink character of the cofactor. These stacking interactions between PLP and aromatic side chains can be found in most PLP-dependent enzymes as it plays an important role in catalyzing the reaction by facilitating transaldimination. Key binding domain residues interacting with PLP.

POLG is located on the q arm of chromosome 15 in position 26.1 and has 23 exons. The POLG gene produces a 140 kDa protein composed of 1239 amino acids. POLG, the protein encoded by this gene, is a member of the DNA polymerase type-A family. It is a mitochondrion nucleiod with an Mg2+ cofactor and 15 turns, 52 beta strands, and 39 alpha helixes.

Factor Va binds to prothrombin and Factor Xa, increasing the rate at which thrombin is produced by four orders of magnitude (10,000x). Inactivation of Factor Va thus practically halts the production of thrombin. Factor VIII, on the other hand, is a cofactor in production of activated Factor X, which in turn converts prothrombin into thrombin. Factor VIIIa augments Factor X activation by a factor of around 200,000.

The coenzyme is the C1 donor in methanogenesis. It is converted to methyl-coenzyme M thioether, the thioether , in the penultimate step to methane formation. Methyl-coenzyme M reacts with coenzyme B, 7-thioheptanoylthreoninephosphate, to give a heterodisulfide, releasing methane: : + HS–CoB -> \+ CoB–S–S–CoM This induction is catalyzed by the enzyme methyl-coenzyme M reductase, which restricts cofactor F430 as the prosthetic group.

Methylmalonic acid (MMA) (conjugate base methylmalonate) is a dicarboxylic acid that is a C-methylated derivative of malonate. The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl-CoA mutase, in a reaction that requires vitamin B12 as a cofactor. In this way, it enters the Krebs cycle, and is thus part of one of the anaplerotic reactions.

FAD plays a major role as an enzyme cofactor along with flavin mononucleotide, another molecule originating from riboflavin. Bacteria, fungi and plants can produce riboflavin, but other eukaryotes, such as humans, have lost the ability to make it. Therefore, humans must obtain riboflavin, also known as vitamin B2, from dietary sources. Riboflavin is generally ingested in the small intestine and then transported to cells via carrier proteins.

Fatty acids accumulate in the liver in a microvesicular pattern that can be seen on biopsy. In the absence of fatty acid metabolism, the body becomes dependent on glucose and glycogen for energy. Octreotide can be used to reduce secretion of insulin by the pancreas, thereby preventing severe hypoglycemia. Inhibition of beta-oxidation of fatty acids, however, also depletes a necessary cofactor for gluconeogenesis.

Methylmalonic acid, if not properly handled by B12, remains in the myelin sheath, causing fragility. Dementia and depression have been associated with this deficiency as well, possibly from the under-production of methionine because of the inability to convert homocysteine into this product. Methionine is a necessary cofactor in the production of several neurotransmitters. Each of those symptoms can occur either alone or along with others.

The NAD+-reducing hydrogenase (soluble hydrogenase, SH) creates a NADH-reducing equivalence by oxidizing hydrogen gas. The SH is a heterohexameric protein with two subunits making up the large and small subunits of the [Ni-Fe] hydrogenase and the other two subunits comprising a reductase module similar to the one of Complex I. The [Ni-Fe] active site oxidized hydrogen gas which transfers electrons to a FMN-a cofactor, then to a [Fe-S] cluster relay of the small hydrogenase subunit and the reductase module, then to another FMN-b cofactor and finally to NAD+. The reducing equivalences are then used for fixing carbon dioxide when C. necator is growing autotrophically. The active site of the SH of C. necator H16 has been extensively studied because C. necator H16 can be produced in large amounts, can be genetically manipulated, and can be analyzed with spectrographic techniques.

MTRR works by catalyzing the following chemical reaction: :2 [methionine synthase]-methylcob(I)alamin + 2 S-adenosylhomocysteine + NADP \rightleftharpoons 2 [methionine synthase]-cob(II)alamin + NADPH + H + 2 S-adenosyl-L-methionine The 3 products of this enzyme are methionine synthase- methylcob(I)alamin, S-adenosylhomocysteine, and NADP, whereas its 4 substrates are methionine synthase-cob(II)alamin, NADPH, H, and S-adenosyl-L-methionine. Scavenger Pathway of Methionine Synthase Reductase to Recover Inactivated Methionine Synthase Physiologically speaking, one crucial enzyme participated in the folate cycle is methionine synthase, which incorporated a coenzyme, cobalamin, also known as Vitamin B12. The coenzyme utilizes its cofactor, cobalt to catalyze the transferring function, in which the cobalt will switch between having 1 or 3 valence electrons, dubbed cob(I)alamin, and cob(III)alamin. Over time, the cob(I)alamin cofactor of methionine synthase becomes oxidized to cob(II)alamin, rendering the enzyme inactive.

Though it is an obligate aerobe, it is able to survive in low-oxygen conditions by utilizing light-energy. H. salinarum express the membrane protein bacteriorhodopsin which acts as a light-driven proton pump. It consists of two parts, the 7-transmembrane protein, bacterioopsin, and the light-sensitive cofactor, retinal. Upon absorption of a photon, retinal changes conformation, causing a conformational change in the bacterioopsin protein which drives proton transport.

Archaerhodopsins are active transporters, using the energy from sunlight to pump H+ ions out of the cell to generate a proton motive force that is used for ATP synthesis. Removal of the retinal cofactor (e.g. by treatment with hydroxylamine) abolishes the transporter function and dramatically alters the absorption spectra of the proteins. The proton pumping ability of AR3 has been demonstrated in recombinant E. coli cells and of AR4 in liposomes.

A glutathione S-transferase gene associated with antioxidant properties isolated from Apis cerana cerana. Scientific National 103: 43 The primary role of GSTs is to catalyze the conjugation of glutathione (GSH) with the electrophilic centers of a wide variety of molecules. The most commonly known substrates of GSTs are xenobiotic synthetic chemicals. There are also classes of GSTs that utilize glutathione as a cofactor rather than a substrate.

Cyclic di-AMP is synthesized by a membrane-bound diadenylate cyclase (also called diadenylyl cyclase, CdA, and DAC) enzyme called CdaA (DacA). DacA condenses two ATP molecules to make c-di-AMP, releasing 2 pyrophosphates in the process. DacA requires a manganese or cobalt metal ion cofactor. Most bacteria possess only one DAC enzyme, but some bacteria like B. subtilis possess two additional DAC enzymes (DisA and CdaS).

The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded protein has cofactor activity for inactivation (through cleavage) of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. The protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization.

The bumped ATP analog N6-cyclopentyl ATP cannot bind wild type v-Src kinase, but can bind its bump- and-hole pair, I338G v-Src kinase. Human protein kinases use ATP as a cofactor to phosphorylate substrate proteins. Kinases play critical roles in complex cell signaling networks. Conserved ATP binding sites and similar catalytic mechanisms pose a challenge to selectively inhibiting a particular kinase to determine its function.

It has been discovered that this protein has a catalytic activity, in other words, it has the ability to increase the speed of chemical reactions which would not occur so fast. It is known to catalysis the following reaction (which requires the following cofactor: Mg(2+)): ATP + RNA(n) ⇄ diphosphate + RNA(n+1) Depending on the surroundings the optimal pH varies from 8 in the cytoplasm to 8.3 in the nucleus.

UDP-N-acetylglucosamine 4,6-dehydratase (configuration-retaining) (, PglF) is an enzyme with systematic name UDP-N-acetyl-alpha-D-glucosamine hydro-lyase (configuration-retaining; UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo- hex-4-ulose-forming). This enzyme catalyses the following chemical reaction : UDP-N-acetyl-alpha-D-glucosamine \rightleftharpoons UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-hex-4-ulose + H2O This enzyme contains NAD+ as a cofactor.

Molybdenum cofactor (Moco) biosynthesis occurs in four steps: (i) the radical-mediated cyclization of nucleotide, guanosine 5'-triphosphate (GTP), to (8S)‑3 ́,8‐cyclo‑7,8‑dihydroguanosine 5 ́‑triphosphate (3 ́,8‑cH2GTP), (ii) the formation of cyclic pyranopterin monophosphate (cPMP) from the 3 ́,8‑cH2GTP, (iii) the conversion of cPMP into molybdopterin (MPT), (iv) the insertion of molybdate into MPT to form Moco. The human enzymes are indicated in parenthesis.

The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene.

Antithrombin is also termed Antithrombin III (AT III). The designations Antithrombin I through to Antithrombin IV originate in early studies carried out in the 1950s by Seegers, Johnson and Fell. Antithrombin I (AT I) refers to the absorption of thrombin onto fibrin after thrombin has activated fibrinogen. Antithrombin II (AT II) refers to a cofactor in plasma, which together with heparin interferes with the interaction of thrombin and fibrinogen.

D-aspartate oxidase is an enzyme that is encoded by the DDO gene. The protein encoded by this gene is a peroxisomal flavoprotein that catalyzes the oxidative deamination of D-aspartate and N-methyl D-aspartate. Flavin adenine dinucleotide or 6-hydroxyflavin adenine dinucleotide can serve as the cofactor in this reaction. Two (or four, according to ) transcript variants encoding different isoforms have been found for this gene.

Autosomal dominant and autosomal recessive forms of the disease have been reported. Mutations in several genes have been shown to cause dopamine-responsive dystonia. The precursor of the neurotransmitter dopamine, L-dopa, is synthesised from tyrosine by the enzyme tyrosine hydroxylase and utilises tetrahydrobiopterin (BH4) as a cofactor. A mutation in the gene GCH1, which encodes the enzyme GTP cyclohydrolase I, disrupts the production of BH4, decreasing dopamine levels (hypodopaminergia).

5,10-Methylenetetrahydrofolate (N5,N10-Methylenetetrahydrofolate; 5,10-CH2-THF) is cofactor in several biochemical reactions. It exists in nature as the diastereoisomer [6R]-5,10-methylene-THF. As an intermediate in one-carbon metabolism, 5,10-CH2-THF interconverts to 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and methenyltetrahydrofolate. It is substrate for the enzyme methylenetetrahydrofolate reductase (MTHFR) It is mainly produced by the reaction of tetrahydrofolate with serine, catalyzed by the enzyme serine hydroxymethyltransferase.

Aminoacylase Reaction Mechanism (click for larger image) Aminoacylase is a metallo-enzyme that needs Zinc (Zn2+) as a cofactor to function. The Zinc ions inside of aminoacylase are each coordinated to histidine, glutamate, aspartate, and water. The Zinc ion polarizes the water, facilitating its deprotonation by a nearby basic residue. The negatively charged hydroxide ion is nucleophilic and attacks the electrophilic carbonyl carbon of the substrate's acyl group.

One of the cleavage fibrinogen products, termed 'desAA-Fibrin', acts as cofactor for the tPA- induced plasminogen activation and an increased fibrinolysis results in return (profibrinolytic activity of ancrod). Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, and facilitates physical and ergo therapy. Finally, ancrod decreases the likelihood of local thrombotic events. These mechanisms also account for ancrod's activity in other diseases.

Two major isoforms of phospholipase D has been identified in mammalian cells: PLD1 and PLD2 (53% sequence homology), each encoded by distinct genes. PLD activity appears to be present in most cell types, with the possible exceptions of peripheral leukocytes and other lymphocytes. Both PLD isoforms require PIP2 as a cofactor for activity. PLD1 and PLD2 exhibit different subcellular localizations that dynamically change in the course of signal transduction.

Calcium acts as a cofactor in PLD isoforms that contain the C2 domain. Binding of Ca2+ to the C2 domain leads to conformational changes in the enzyme that strengthen enzyme-substrate binding, while weakening the association with phosphoinositides. In some plant isoenzymes, such as PLDβ, Ca2+ may bind directly to the active site, indirectly increasing its affinity for the substrate by strengthening the binding of the activator PIP2.

Cofactors typically differ from ligands in that they often derive their function by remaining bound. Cofactors can be divided into two types: inorganic ions and complex organic molecules called coenzymes. Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. (Note that some scientists limit the use of the term "cofactor" to inorganic substances; both types are included here.) Coenzymes are further divided into two types.

PARP1 is involved in base excision repair (BER), single- and double-strand break repair, and chromosomal stability. It is also involved in transcriptional regulation through its facilitation of protein–protein interactions. PARP1 uses NAD+ in order to perform its function in apoptosis. If a PARP becomes overactive the cell will have decreased levels of NAD+ cofactor as well as decreased levels of ATP and thus will undergo necrosis.

As prolyl hydroxylase requires ascorbate as a cofactor to function, its absence compromises the enzyme’s activity. The resulting decreased hydroxylation leads to the disease condition known as scurvy. Since stability of collagen is compromised in scurvy patients, symptoms include weakening of blood vessels causing purpura, petechiae, and gingival bleeding. Hypoxia-inducible factor (HIF) is an evolutionarily conserved transcription factor that allows the cell to respond physiologically to decreases in oxygen.

In enzymology, a peptide-aspartate beta-dioxygenase (), a member of the alpha- ketoglutarate-dependent hydroxylases superfamily, is an enzyme that catalyzes the chemical reaction :peptide-L-aspartate + 2-oxoglutarate + O2 \rightleftharpoons peptide-3-hydroxy-L-aspartate + succinate + CO2 The 3 substrates of this enzyme are peptide-L-aspartate, 2-oxoglutarate, and O2, whereas its 3 products are peptide-3-hydroxy-L-aspartate, succinate, and CO2. It employs one cofactor, iron.

Accumulated succinate inhibits dioxygenases, such as histone and DNA demethylases or prolyl hydroxylases, by competitive inhibition. Thus, succinate modifies the epigenic landscape and regulates gene expression. Accumulation of either fumarate or succinate reduces the activity of 2-oxogluterate-dependent dioxygenases, including histone and DNA demethylases, prolyl hydroxylases and collagen prolyl-4-hydroxyalses, through competitive inhibition. 2-oxoglutarate-dependent dioxygenases require an iron cofactor to catalyze hydroxylations, desaturations and ring closures.

In enzymology, a glucoside 3-dehydrogenase () is an enzyme that catalyzes the chemical reaction :sucrose + acceptor \rightleftharpoons 3-dehydro-alpha-D- glucosyl-beta-D-fructofuranoside + reduced acceptor Thus, the two substrates of this enzyme are sucrose and acceptor, whereas its two products are 3-dehydro-alpha-D-glucosyl-beta-D-fructofuranoside and reduced acceptor. This enzyme participates in galactose metabolism and starch and sucrose metabolism. It employs one cofactor, FAD.

In enzymology, a 1-hydroxy-2-naphthoate 1,2-dioxygenase () is an enzyme that catalyzes the chemical reaction :1-hydroxy-2-naphthoate + O2 \rightleftharpoons (3Z)-4-(2-carboxyphenyl)-2-oxobut-3-enoate Thus, the two substrates of this enzyme are 1-hydroxy-2-naphthoate and O2, whereas its product is (3Z)-4-(2-carboxyphenyl)-2-oxobut-3-enoate. This enzyme participates in naphthalene and anthracene degradation. It employs one cofactor, iron.

This enzyme contains a short-chain dehydrogenase domain that contains a characteristic 3-layer (αβα) sandwich known as a Rossmann fold. The human enzyme contains 327 amino acids and exists as a homodimer with two identical subunits of 34.5 kDa The N-terminal short- chain dehydrogenase domain contains binding site for the NADP+/NADPH cofactor. A narrow, hydrophobic C-terminal domain contains a binding pocket for the steroid substrate.

Typical type II restriction enzymes differ from type I restriction enzymes in several ways. They form homodimers, with recognition sites that are usually undivided and palindromic and 4–8 nucleotides in length. They recognize and cleave DNA at the same site, and they do not use ATP or AdoMet for their activity—they usually require only Mg2+ as a cofactor. These enzymes cleave the phosphodiester bond of double helix DNA.

Coagulation (FIX is on left) Factor IX deficiency leads to an increased propensity for haemorrhage, which can be either spontaneously or in response to mild trauma. Factor IX deficiency can cause interference of the coagulation cascade, thereby causing spontaneous hemorrhage when there is trauma. Factor IX when activated activates factor X which helps fibrinogen to fibrin conversion. Factor IX becomes active eventually in coagulation by cofactor factor VIII (specifically IXa).

Mutations in this gene have been associated with Leber's congenital amaurosis type 2 (LCA2) and retinitis pigmentosa (RP). RPE65 mutations are the most commonly detected mutations in LCA patients in Denmark. The vast majority of RPE65 mutations in patients with LCA2 and RP occur in the beta-propeller regime and are believed to inhibit proper protein folding and iron cofactor binding. Particularly common propeller mutation sites are Tyr368 and His182.

Serine palmitoyltransferase, long chain base subunit 1, also known as SPTLC1, is a protein which in humans is encoded by the SPTLC1 gene. Serine palmitoyltransferase, which consists of two different subunits, is the initial enzyme in sphingolipid biosynthesis. It converts L-serine and palmitoyl CoA to 3-oxosphinganine with pyridoxal 5'-phosphate as a cofactor. The product of this gene is the long chain base subunit 1 of serine palmitoyltransferase.

Pyridoxal kinase is an enzyme that in humans is encoded by the PDXK gene. The protein encoded by this gene phosphorylates vitamin B6, a step required for the conversion of vitamin B6 to pyridoxal-5-phosphate, an important cofactor in intermediary metabolism. The encoded protein is cytoplasmic and probably acts as a homodimer. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

L-carnitine is an amino acid and precursor of acetyl-L-carnitine which is a mitochondrial cofactor. It acts to help with overall mitochondrial function as well as lipid metabolism which is an important function of mitochondria. This is important as an increase in mitochondrial function will help to reduce the rates of oxidative reactions in the brain which overall decrease damage to DNA and stimulates better cognitive function.

The N-domain consists of two sub-domains of roughly equal size: the N-terminal double Y-barrel and a C-terminal b-barrel (Figure 3). Figure 3- Structure of the N-domain of p97. The N-domain is depicted as a molecular surface superimposed to a ribbon representation. Structural studies show that many cofactor proteins bind to the N-domain at a cleft formed between the two sub-domains.

In normal patients, only one percent of dietary tryptophan is converted to serotonin; however, in patients with carcinoid syndrome, this value may increase to 70%. Carcinoid syndrome thus may produce niacin deficiency and clinical manifestations of pellagra. Anti- tuberculosis medication tends to bind to vitamin B6 and reduce niacin synthesis, since B6 (pyridoxine) is a required cofactor in the tryptophan-to- niacin reaction. Several therapeutic drugs can provoke pellagra.

GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. Mutations in the GM2A gene cause AB variant. The GM2A gene provides instructions for making a protein called the GM2 activator. This protein is a cofactor that is required for the normal function of beta-hexosaminidase A. The disease is usually fatal by early childhood.

Cyclic pyranopterin monophosphate (cPMP) is an experimental treatment for molybdenum cofactor deficiency type A, which was developed by José Santamaría- Araujo and Guenter Schwarz at the German universities TU Braunschweig and the University of Cologne.Doctors risk untried drug to stop baby’s brain dissolving, TimesOnline, November 5, 2009 cPMP is a precursor to molybdopterin, which is required for the enzyme activity of sulfite oxidase, xanthine dehydrogenase/oxidase and aldehyde oxidase.

An inactive enzyme without the cofactor is called an apoenzyme, while the complete enzyme with cofactor is called a holoenzyme. (Note that the International Union of Pure and Applied Chemistry (IUPAC) defines "coenzyme" a little differently, namely as a low-molecular-weight, non-protein organic compound that is loosely attached, participating in enzymatic reactions as a dissociable carrier of chemical groups or electrons; a prosthetic group is defined as a tightly bound, nonpolypeptide unit in a protein that is regenerated in each enzymatic turnover.) Some enzymes or enzyme complexes require several cofactors. For example, the multienzyme complex pyruvate dehydrogenase at the junction of glycolysis and the citric acid cycle requires five organic cofactors and one metal ion: loosely bound thiamine pyrophosphate (TPP), covalently bound lipoamide and flavin adenine dinucleotide (FAD), cosubstrates nicotinamide adenine dinucleotide (NAD+) and coenzyme A (CoA), and a metal ion (Mg2+). Organic cofactors are often vitamins or made from vitamins.

Its expression is induced by decreased sterol concentrations via sterol regulatory binding proteins (SREBP). There is also evidence that its activity may be regulated by tissue specific transcription, and alternative splicing. As outlined above, the enzyme DHCR7 catalyzes the reduction of 7DHC to cholesterol, as well as the reduction of 7-dehydrodesmosterol to desmosterol. It requires NADPH as a cofactor for this reduction, and may involve the activity of cytochrome-P450 oxidoreductase.

GC or AC are more effective. Furthermore, the RNA cleavage rates have been shown to increase after the introduction of intercalators or the substitution of deoxyguanine with deoxyinosine at the junction of the catalytic loop. Specifically, the addition of 2’-O-methyl modifications to the catalytic proved to significantly increase the cleavage rate both in vitro and in vivo. Other notable deoxyribozyme ribonucleases are those that are highly selective for a certain cofactor.

MPO is a member of the XPO subfamily of peroxidases and produces hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion (Cl−) (or hypobromous acid if Br- is present) during the neutrophil's respiratory burst. It requires heme as a cofactor. Furthermore, it oxidizes tyrosine to tyrosyl radical using hydrogen peroxide as an oxidizing agent. Hypochlorous acid and tyrosyl radical are cytotoxic, so they are used by the neutrophil to kill bacteria and other pathogens.

2,4 Dienoyl-CoA reductase also known as DECR1 is an enzyme which in humans is encoded by the DECR1 gene which resides on chromosome 8. This enzyme catalyzes the following reactions File:Dienoyl-CoA reductase reaction cis-trans.svg DECR1 participates in the beta oxidation and metabolism of polyunsaturated fatty enoyl-CoA esters. Specifically, it catalyzes the reduction of 2,4 dienoyl-CoA thioesters of varying length by NADPH cofactor to 3-trans-enoyl- CoA of equivalent length.

Crystal structure of [Fe] hydrogenase 5,10-methenyltetrahydromethanopterin hydrogenase (EC 1.12.98.2) found in methanogenic Archaea contains neither nickel nor iron- sulfur clusters but an iron-containing cofactor that was recently characterized by X-ray diffraction. Unlike the other two types, [Fe]-only hydrogenases are found only in some hydrogenotrophic methanogenic archaea. They also feature a fundamentally different enzymatic mechanism in terms of redox partners and how electrons are delivered to the active site.

Main distributions of different types of Flavin-containing Monooxygenases (FMO) in adult human tissues. Expression of each type of FMO relies on several factors including, cofactor supply, physiological & environmental factors, as well as diet. Because of these factors, each type of FMO is expressed differently depending on the species and tissue. In humans, expression of FMO's is mainly concentrated to the human liver, lungs, and kidneys, where most of the metabolism of xenobiotics occur.

3-Dehydroquinate synthase utilizes a complex multi-step mechanism that includes alcohol oxidation, phosphate β-elimination, carbonyl reduction, ring opening, and intramolecular aldol condensation. Dehydroquinate synthase requires NAD+ and a cobalt cofactor to catalyze the conversion of 3-deoxy-D-arabino-heptulosonate 7-phosphate into 3-dehydroquinate. Dehydroquinate synthase is of particular interest because of its complicated activity relative to its small size. In most bacteria, this enzyme has only one function.

In higher plants, nickel is absorbed by plants in the form of Ni2+ ion. Nickel is essential for activation of urease, an enzyme involved with nitrogen metabolism that is required to process urea. Without nickel, toxic levels of urea accumulate, leading to the formation of necrotic lesions. In lower plants, nickel activates several enzymes involved in a variety of processes, and can substitute for zinc and iron as a cofactor in some enzymes.

This enzyme belongs to the family of hydrolases, specifically those acting on phosphoric monoester bonds. 512x512px The hydrolysis of phosphoglycolate begins with the nucleophilic attack by an aspartate residue on the electrophilic phosphorus of the phosphoglycolate. The susceptibility of the bond between phosphate and glycolate is heightened by two key interactions. An interaction with the cofactor, Mg2+, helps polarize the phosphate-oxygen bond and therefore increases the electrophilicity of the phosphorus atom.

This enzymatic step requires vitamin C as a cofactor. In scurvy, the lack of hydroxylation of prolines and lysines causes a looser triple helix (which is formed by three alpha peptides). ## Glycosylation occurs by adding either glucose or galactose monomers onto the hydroxyl groups that were placed onto lysines, but not on prolines. ## Once these modifications have taken place, three of the hydroxylated and glycosylated propeptides twist into a triple helix forming procollagen.

The NADPH cofactor is situated at the top of the β/α barrel, with the nicotinamide ring projects down in the center of the barrel and pyrophosphate straddling the barrel lip. Mechanism of NADPH- dependent conversion of glucose to sorbitol. Note the hydride transfer from NADPH to the carbonyl carbon of the aldose. Depiction of NADPH in extended confirmation and hydrogen bonded to the residues physically near the active site of the enzyme.

Nerve impulses increase the synthesis of PNMT mRNA by affecting certain promoter sequences. Stress immobilization for a few hours has also been shown to increase PNMT activity in rats. This treatment takes about one week to manifest a difference in PNMT levels. SAM not only acts as a cofactor for PNMT, but also helps to stabilize the enzyme and increase the half life by making it more resistant to being cut by trypsin protease.

In molecular biology, the copper type II ascorbate-dependent monooxygenases are a class of enzymes that require copper as a cofactor and which use ascorbate as an electron donor. This family contains two related enzymes, dopamine beta-monooxygenase and peptidylglycine alpha-amidating monooxygenase . There are a few regions of sequence similarities between these two enzymes, two of these regions contain clusters of conserved histidine residues which are most probably involved in binding copper.

This enzyme participates in lipoic acid metabolism, where it performs the final step in lipoic acid biosynthesis. Lipoic acid is a cofactor that has different functions within different organisms. The lipoic acid generation in yeast cells increases the number of divisions in the cells as well as protects yeast cells from hydrogen peroxide. Lipoic acid is an important co-factor in many enzyme systems, and one of them is the pyruvate dehydrogenase complex.

Zinc is an essential cofactor for more than 50 classes of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. Zinc cannot passively diffuse across cell membranes and requires specific transporters, such as SLC39A7, to enter the cytosol from both the extracellular environment and from intracellular storage compartments. ZIP7 is a membrane transport protein of the endoplasmic reticulum.

Tetrahydrobiopterin deficiency (THBD, BH4D) is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained normally through the diet, but can be harmful if excess levels build up, causing intellectual disability and other serious health problems. In healthy individuals, it is metabolised (hydroxylated) into tyrosine, another amino acid, by phenylalanine hydroxylase. However, this enzyme requires tetrahydrobiopterin as a cofactor and thus its deficiency slows phenylalanine metabolism.

The purine biosynthesis enzymes can be co-purified under certain conditions. A complex of two particular pathway enzymes GART and ATIC can be isolated with cofactor production enzyme C1THF synthase and SHMT1. Kinetic studies show evidence of substrate channeling between PPAT and GART, but evidence could not be obtained for their physical protein-protein interaction. Thus far, isolation of a multienzyme complex inclusive of all purine biosynthesis enzymes has not been achieved.

Selenenic acids derived from selenocysteine are involved in cell signaling and certain enzymatic processes. The best known selenoenzyme, glutathione peroxidase (GPx), catalyzes the reduction of peroxides by glutathione (GSH). The selenenic acid intermediate (E-SeOH) is formed upon oxidation of the catalytically active selenol (E-SeH) by hydrogen peroxide. This selenenic acid derivative of the peroxidase then reacts with a thiol-containing cofactor (GSH) to generate the key intermediate selenenyl sulfide (E-SeSG).

In this method (also known as VtC XES = Valence-to-Core X-ray Emission Spectroscopy), one monitors the resultant fluorescence after a valence electron refills the ionized metal 1s core hole. As such, valence XES spectra provide a map of ligand ionization energies, and provides information on both ligand identity and protonation state. A prominent application of this method its use to identify the central carbon atom in FeMo cofactor of Nitrogenase (see section Nitrogenase).

QPNC-PAGE, or quantitative preparative native continuous polyacrylamide gel electrophoresis, is a bioanalytical, high-resolution and highly accurate technique applied in biochemistry and bioinorganic chemistry to separate proteins quantitatively by isoelectric point. This standardized variant of native gel electrophoresis is used by biologists to isolate biomacromolecules in solution, for example, active or native metalloproteins in biological samples or properly and improperly folded metal cofactor-containing proteins or protein isoforms in complex protein mixtures.

SAM-VI is a member of the riboswitch family. It is predominantly found in Bifidobacterium and exhibits some similarities to the SAM-III (Smk box) riboswitch class, but lacks most of the highly-conserved nucleotides of SAM- III class. SAM-VI aptamers bind the cofactor S-adenosylmethinine SAM (a key metabolite in sulphur metabolism) and discriminate strongly against S-adenosylhomocysteine SAH. The class was discovered by further analysis of Bifido-meK motif RNAs.

Although an atomic resolution structure for intact factor H has not yet been determined, low resolution techniques indicate that it may be bent back in solution. Information available to date indicates that CCP modules 1–4 is responsible for the cofactor and decay acceleration activities of factor H, whereas self/non-self discrimination occurs predominantly through GAG binding to CCP modules 7 and/or GAG or sialic acid binding to 19–20.

RDH13 is most closely related to the NADP+-dependent microsomal enzymes RDH11, RDH12 and RDH14. Purified RDH13 acts on retinoids in an oxidative reductive manner, and strongly prefers the cofactor NADPH over NADH. Moreover, RDH13 is much has much more efficient reductase activity than dehydrogenase activity. RDH13 as a retinaldehyde reductase is significantly less active than that of a related protein RDH11, primarily because of the much higher Km value for retinaldehyde.

Biopterins are pterin derivatives which function as endogenous enzyme cofactors in many species of animals and in some bacteria and fungi. Biopterins act as cofactors for aromatic amino acid hydroxylases (AAAH), which are involved in the synthesis of a number of neurotransmitters including dopamine, norepinephrine, epinepherine, and serotonin, along with several trace amines. Nitric oxide synthesis also uses biopterin derivatives as cofactors. In humans, tetrahydrobiopterin is the endogenous cofactor for AAAH enzymes.

Methionine can be regenerated from homocysteine via (4) methionine synthase in a reaction that requires vitamin B12 as a cofactor. Homocysteine can also be remethylated using glycine betaine (NNN-trimethyl glycine, TMG) to methionine via the enzyme betaine-homocysteine methyltransferase (E.C.2.1.1.5, BHMT). BHMT makes up to 1.5% of all the soluble protein of the liver, and recent evidence suggests that it may have a greater influence on methionine and homocysteine homeostasis than methionine synthase.

The basic residue or cofactor deprotonates the alpha carbon, and FAD accepts the hydride from the beta carbon, oxidizing the bound succinate to fumarate—refer to image 6. In E1cb, an enolate intermediate is formed, shown in image 7, before FAD accepts the hydride. Further research is required to determine which elimination mechanism succinate undergoes in Succinate Dehydrogenase. Oxidized fumarate, now loosely bound to the active site, is free to exit the protein.

The first organic cofactor to be discovered was NAD+, which was identified by Arthur Harden and William Youndin 1906. They noticed that adding boiled and filtered yeast extract greatly accelerated alcoholic fermentation in unboiled yeast extracts. They called the unidentified factor responsible for this effect a coferment. Through a long and difficult purification from yeast extracts, this heat-stable factor was identified as a nucleotide sugar phosphate by Hans von Euler-Chelpin.

The succinate dehydrogenase complex showing several cofactors, including flavin, iron-sulfur centers, and heme. A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's activity as a catalyst, a substance that increases the rate of a chemical reaction. Cofactors can be considered "helper molecules" that assist in biochemical transformations. The rates at which these happen are characterized in an area of study called enzyme kinetics.

This enzyme belongs to the family of oxidoreductases, to be specific, those acting on paired donors, with O2 as the oxidant. Kynurenine 3-monooxygenase catalyzes the insertion of molecular oxygen into the aromatic ring of kynurenine to produce 3-hydroxy--kynurenine. It employs one cofactor, FAD. Kynurenine 3-monooxygenase serves as an important branch point in the kynurenine pathway and, as a result, is an attractive drug target for immunological, neurodegenerative, and neuroinflammatory diseases.

In enzymology, an acyl-[acyl-carrier-protein] desaturase () is an enzyme that catalyzes the chemical reaction :stearoyl-[acyl-carrier-protein] + reduced acceptor + O2 \rightleftharpoons oleoyl-[acyl-carrier-protein] + acceptor + 2 H2O The systematic name of this enzyme class is acyl-[acyl-carrier-protein], hydrogen-donor:oxygen oxidoreductase. Other names in common use include stearyl acyl carrier protein desaturase, and stearyl-ACP desaturase. This enzyme participates in polyunsaturated fatty acid biosynthesis. It employs one cofactor, ferredoxin.

The kinase complex containing this cyclin and the elongation factor can interact with, and act as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and was shown to be both necessary and sufficient for full activation of viral transcription. This cyclin and its kinase partner were also found to be involved in the phosphorylation and regulation of the carboxy-terminal domain (CTD) of the largest RNA polymerase II subunit.

In phenylalanine hydroxylase over 300 different mutations throughout the structure cause phenylketonuria. Phenylalanine substrate and tetrahydrobiopterin coenzyme in black, and Fe2+ cofactor in yellow. () Since the tight control of enzyme activity is essential for homeostasis, any malfunction (mutation, overproduction, underproduction or deletion) of a single critical enzyme can lead to a genetic disease. The malfunction of just one type of enzyme out of the thousands of types present in the human body can be fatal.

Consider the reaction of peptide bond hydrolysis catalyzed by a pure protein α-chymotrypsin (an enzyme acting without a cofactor), which is a well-studied member of the serine proteases family, see. We present the experimental results for this reaction as two chemical steps: where S1 is a polypeptide, P1 and P2 are products. The first chemical step () includes the formation of a covalent acyl-enzyme intermediate. The second step () is the deacylation step.

Sulfite oxidase is required to metabolize the sulfur-containing amino acids cysteine and methionine in foods. Lack of functional sulfite oxidase causes a disease known as sulfite oxidase deficiency. This rare but fatal disease causes neurological disorders, mental retardation, physical deformities, the degradation of the brain, and death. Reasons for the lack of functional sulfite oxidase include a genetic defect that leads to the absence of a molybdopterin cofactor and point mutations in the enzyme.

Malate dehydrogenase, mitochondrial also known as malate dehydrogenase 2 is an enzyme that in humans is encoded by the MDH2 gene. Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria.

The resulting decarboxylated tryptophan analog is tryptamine. Tryptamine then undergoes a transmethylation (step 2): the enzyme indolethylamine-N-methyltransferase (INMT) catalyzes the transfer of a methyl group from cofactor S-adenosyl- methionine (SAM), via nucleophilic attack, to tryptamine. This reaction transforms SAM into S-adenosylhomocysteine (SAH), and gives the intermediate product N-methyltryptamine (NMT). NMT is in turn transmethylated by the same process (step 3) to form the end product N,N-dimethyltryptamine.

Glutaredoxins (also known as Thioltransferase) are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. In humans this oxidation repair enzyme is also known to participate in many cellular functions, including redox signaling and regulation of glucose metabolism. Glutaredoxins are oxidized by substrates, and reduced non- enzymatically by glutathione. In contrast to thioredoxins, which are reduced by thioredoxin reductase, no oxidoreductase exists that specifically reduces glutaredoxins.

Figure 1 As depicted in Figure 1, the Elk1 protein is composed of several domains. Localized in the N-terminal region, the A domain is required for the binding of Elk1 to DNA. This region also contains a nuclear localization signal (NLS) and a nuclear export signal (NES), which are responsible for nuclear import and export, respectively. The B domain allows Elk1 to bind to a dimer of its cofactor, serum response factor (SRF).

This enzyme participates in bile acid biosynthesis. The substrate-binding domain found in some bacterial cholesterol oxidases is composed of an eight-stranded mixed beta-pleated sheet and six alpha-helices. This domain is positioned over the isoalloxazine ring system of the FAD cofactor bound by the FAD-binding domain and forms the roof of the active site cavity, allowing for catalysis of oxidation and isomerisation of cholesterol to cholest-4-en-3-one.

Biosynthesis: The enzyme 3-dehydroquinate dehydratase uses 3-dehydroquinate to produce 3-dehydroshikimate and H2O. 3-Dehydroshikimate is then reduced to shikimic acid by the enzyme shikimate dehydrogenase, which uses nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. :Biosynthesis of shikimic acid from 3-dehydroquinate Gallic acid is also formed from 3-dehydroshikimate by the action of the enzyme shikimate dehydrogenase to produce 3,5-didehydroshikimate. This latter compound spontaneously rearranges to gallic acid.

This enzyme participates in 8 metabolic pathways: alanine and aspartate metabolism, methionine metabolism, valine, leucine and isoleucine degradation, tyrosine metabolism, phenylalanine metabolism, tryptophan metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and alkaloid biosynthesis. It employs one cofactor, flavin adenine dinucleotide (FAD). The enzyme binds to FAD in the first step of the catalytic process, thereby reducing FAD to FADH2. The FAD is regenerated from FADH2 by oxidation as a result of O2 being reduced to H2O2.

BH4 is concomitantly shifted toward the iron atom, although the pterin cofactor remains in the second coordination sphere. On the other hand, a competing model based on NMR and molecular modeling analyses suggests that all coordinated water molecules are forced out of the active site during the catalytic cycle while BH4 becomes directly coordinated to iron. As discussed above, resolving this discrepancy will be important for determining the exact mechanism of PAH catalysis.

At the center is the helical ribonucleocapsid, which consists of the genomic RNA wrapped around a polymer of nucleoproteins (NP). Associated with the ribonucleoprotein is the RNA-dependent RNA polymerase (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein is embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles are surrounded by a lipid membrane derived from the host cell membrane.

The carboxyphosphate then exothermically decomposes into carbon dioxide and inorganic phosphate, at this point making this an irreversible reaction. Finally, after the decomposition, the carbon dioxide is attacked by the enolate to form oxaloacetate. The metal cofactor is necessary to coordinate the enolate and carbon dioxide intermediates; the CO2 molecule is only lost 3% of the time. The active site is hydrophobic to exclude water, since the carboxyphosphate intermediate is susceptible to hydrolysis.

TRIM21 is an intracellular antibody effector in the intracellular antibody-mediated proteolysis pathway. It recognizes Fc domain and binds to immunoglobulin G, immunoglobuin A and immunoglobulin M on antibody marked non-enveloped virions which have infected the cell. Either by autoubiquitination or by ubiquitination of a cofactor, it is then responsible for directing the virions to the proteasome. TRIM21 itself is not degraded in the proteasome unlike both the viral capsid and the bound antibody.

Peptidoglycan is an essential structural component of the bacterial cell wall. The peptidoglycan layer is also responsible for the rigidity of the cell wall. This process, in which MurI helps catalyze the interconversion of glutamate enantiomers, like L-Glutamate, into the essential D-glutamate, is also cofactor independent. As such it can proceed without needing an additional source, which would bind to an allosteric site, altering the enzyme shape to assist in catalyzing the reaction.

In her study, published in September 2016, Hammes-Schiffer contributed towards discovering the effects of the active site of the magnesium ion in the Scissile Phosphate cofactor complex. She discovered that rather than the magnesium ion lying in the center of the complex, the ion lies in a separate site, termed the Hoogsteen Face, where it lowers the pKa of the complex in order to facilitate a deprotonation reaction necessary for a self-cleavage reaction.

In both types of histone methyltransferases, S-Adenosyl methionine (SAM) serves as a cofactor and methyl donor group. The genomic DNA of eukaryotes associates with histones to form chromatin. The level of chromatin compaction depends heavily on histone methylation and other post-translational modifications of histones. Histone methylation is a principal epigenetic modification of chromatin that determines gene expression, genomic stability, stem cell maturation, cell lineage development, genetic imprinting, DNA methylation, and cell mitosis.

In enzymology, a D-serine ammonia-lyase () is an enzyme that catalyzes the chemical reaction :D-serine \rightleftharpoons pyruvate + NH3 Hence, this enzyme has one substrate, D- in common use include D-hydroxyaminoacid dehydratase, D-serine dehydrase, D-hydroxy amino acid dehydratase, D-serine hydrolase, D-serine dehydratase (deaminating), D-serine deaminase, and D-serine hydro-lyase (deaminating). This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, pyridoxal phosphate.

This form of NAD is one of three products that are formed from non-enzymatic reduction of β-NAD in addition to 4-dihydroNAD (β-NADH), 2-dihydroNAD (2DHNAD). Both 2DHNAD and 6DHNAD were shown to be substrates for renalase. These molecules react rapidly to reduce the enzyme's flavin cofactor forming β-NAD. The renalase flavin then delivers the electrons harvested to O2 (dioxygen) forming H2O2 (hydrogen peroxide), completing the catalytic cycle.

Ethanolamine utilization (EUT) BMCs are encoded in many diverse types of bacteria. Ethanolamine is cleaved to ammonia and acetaldehyde through the action of ethanolamine-ammonia lyase, which also requires vitamin B12 as a cofactor. Acetaldehyde is fairly volatile, and mutants deficient in the BMC shell have been observed to have a growth defect and release excess amounts of acetaldehyde. It has been proposed that sequestration of acetaldehyde in the metabolosome prevents its loss by volatility.

Coenzyme B is a coenzyme required for redox reactions in methanogens. The full chemical name of coenzyme B is 7-mercaptoheptanoylthreoninephosphate. The molecule contains a thiol, which is its principal site of reaction. Coenzyme B reacts with 2-methylthioethanesulfonate (methyl-Coenzyme M, abbreviated ), to release methane in methanogenesis: : + HS–CoB -> \+ CoB–S–S–CoM This conversion is catalyzed by the enzyme methyl coenzyme M reductase, which contains cofactor F430 as the prosthetic group.

FAD is converted between these states by accepting or donating electrons. FAD, in its fully oxidized form, or quinone form, accepts two electrons and two protons to become FADH2 (hydroquinone form). The semiquinone (FADH·) can be formed by either reduction of FAD or oxidation of FADH2 by accepting or donating one electron and one proton, respectively. Some proteins, however, generate and maintain a superoxidized form of the flavin cofactor, the flavin-N(5)-oxide.

A key event in the final stages of blood coagulation is the conversion of fibrinogen into fibrin by the serine protease enzyme thrombin. Thrombin is produced from prothrombin, by the action of an enzyme, prothrombinase (Factor Xa along with Factor Va as a cofactor), in the final states of coagulation. Fibrin is then cross linked by factor XIII (Fibrin Stabilizing Factor) to form a blood clot. The principal inhibitor of thrombin in normal blood circulation is antithrombin.

In the field of enzymology, a CDP-glucose 4,6-dehydratase is an enzyme that catalyzes the chemical reaction :CDP-glucose \rightleftharpoons CDP-4-dehydro-6-deoxy-D-glucose + H2O Hence, this enzyme has one substrate, CDP-glucose, and two products, CDP-4-dehydro-6-deoxy-D-glucose and H2O. This enzyme belongs to the family of lyases, specifically the hydro-lyases, which cleave carbon-oxygen bonds. This enzyme participates in starch and sucrose metabolism. It employs one cofactor, NAD+.

The iota class is the most recent class of CAs described. It has been discovered in the marine diatom Thalassiosira pseudonana, and is widespread among marine phytoplankton. In diatoms, the ι-CA is essential for the CO2-concentrating mechanisms and - in contrast to other CA classes - it can use manganese instead of zinc as metal cofactor. Homologs of the ι-CA have been also confirmed in gram-negative bacteria, where can be present as a protein homodimer.

These enzymes contain the amino acid sequence motif PD-(D/E)XK to coordinate Mg2+, a cation required to cleave DNA in most type II restriction endonucleases. The cofactor Mg2+ is believed to bind water molecules and carry them to the catalytic sites of the enzymes, among other cations. Unlike most documented type II restriction endonucleases, HindIII is unique in that it has little to no catalytic activity when Mg2+ is substituted for other cofactors, such as Mn2+.

They possess a number of accessory proteins including ADF/cofilin, which has a molecular weight of 16kDa and is coded for by a single gene, called COF1; Aip1, a cofilin cofactor that promotes the disassembly of microfilaments; Srv2/CAP, a process regulator related to adenylate cyclase proteins; a profilin with a molecular weight of approximately 14 kDa that is related/associated with actin monomers; and twinfilin, a 40 kDa protein involved in the organization of patches.

The canonical squalene monooxygenase is a flavoprotein monooxygenase. Flavoprotein monooxygenase form flavin hydroperoxides at the enzyme active site, which then transfer the terminal oxygen atom of the hydroperoxide to the substrate. Squalene monooxygenase differs from other flavin monooxygenases in that the oxygen is inserted as an epoxide rather than as a hydroxyl group. Squalene monooxygenase contains a loosely bound FAD flavin and obtains electrons from NADPH-cytochrome P450 reductase, rather than binding the nicotinamide cofactor NADPH directly.

These agents known as vitamin K antagonists (VKA), inhibit the vitamin K-dependent carboxylation of Factors II (prothrombin), VII, IX, X in the hepatocyte. This carboxylation after the translation is essential for the physiological activity. Heparin (unfractionated heparin) and its derivatives low molecular weight heparin (LMWH) bind to a plasma cofactor, antithrombin (AT) to inactivate several coagulation factors IIa, Xa, XIa and XIIa. The affinity of unfractionated heparin and the various LMWHs for Factor Xa varies considerably.

The implication of phosphoglycolate phosphatase in the regulation of 2,3-PGA suggests the importance of having a functional version of the enzyme. In all animal tissues, 2,3-PGA is important as the cofactor of the glycolytic enzyme, phosphoglycerate mutase. More important, the synthesis and breakdown of 2,3-PGA is critical to regulation of hemoglobin’s binding affinity to oxygen, and an increase in its concentration leads to increased tissue oxygenation while a decrease may lead to tissue hypoxia.

FGF21 also protects animals from diet-induced obesity when overexpressed in transgenic mice and lowers blood glucose and triglyceride levels when administered to diabetic rodents. Treatment of animals with FGF21 results in increased energy expenditure, fat utilization and lipid excretion. β-Klotho () functions as a cofactor essential for FGF21 activity. In cows plasma FGF21 was nearly undetectable in late pregnancy (LP), peaked at parturition, and then stabilized at lower, chronically elevated concentrations during early lactation (EL).

S-adenosyl-L-homocysteine hydrolase () (AdoHcyase) is an enzyme of the activated methyl cycle, responsible for the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine. AdoHcyase is a ubiquitous enzyme which binds and requires NAD+ as a cofactor. AdoHcyase is a highly conserved protein of about 430 to 470 amino acids. The family contains a glycine-rich region in the central part of AdoHcyase; a region thought to be involved in NAD-binding.

Model of the replicase- transcriptase complex of a coronavirus. RdRp for replication (red), ExoN for proofreading (dark blue), ExoN cofactor (yellow), RBPs to avoid secondary structure (light blue), RNA sliding clamp for processivity and primase domain for priming (green/orange), and a helicase to unwind RNA (downstream). A number of the nonstructural replication proteins coalesce to form a multi- protein replicase-transcriptase complex (RTC). The main replicase- transcriptase protein is the RNA-dependent RNA polymerase (RdRp).

3-O-Methyldopa (3-OMD) is one of the most important metabolites of L-DOPA, a drug used in the treatment of the Parkinson's disease. 3-O-methyldopa is produced by the methylation of L-DOPA by the enzyme catechol-O- methyltransferase. The necessary cofactor for this enzymatic reaction is s-adenosyl methionine (SAM) Its half-life (approximately 15 hours) is longer than L-DOPA's half-life, which is about one hour.Parkinson’s Disease and movement disorders.

Given that there are three pathways to convert aspartate to lysine, this is clearly an essential process for the cell, particularly in building cell walls in Gram-positive bacteria. There is no process for producing lysine in humans, but ornithine decarboxylase shares many similarities with DAPDC. Both enzymes use PLP as a cofactor and have similar structures forming the active sites. However, DAPDC differs in that it decarboxylates at the D-stereocenter and is highly stereospecific.

In enzymology, an aminobenzoate decarboxylase () is an enzyme that catalyzes the chemical reaction :4(or 2)-aminobenzoate \rightleftharpoons aniline + CO2 Thus, the two substrates of this enzyme are 4-aminobenzoate and 2-aminobenzoate, whereas its two products are aniline and CO2. This enzyme belongs to the family of lyases, specifically the carboxy-lyases, which cleave carbon-carbon bonds. The systematic name of this enzyme class is aminobenzoate carboxy-lyase (aniline-forming). It employs one cofactor, pyridoxal phosphate.

Chemical structure of cannbigerolic acid (CBGA), the substrate for THCA synthase. THCA synthase, a flavoprotein, uses a flavin adenine dinucleotide (FAD) cofactor to catalyze the oxidative cyclization of the monoterpene moiety of cannabigerolic acid (CBGA). Similar cyclization reactions occur in monoterpene biosynthesis from geranyl pyrophosphate, but are not oxidative. THCA synthase exhibits no catalytic activity against cannabigerol, which lacks a carboxyl group compared to CBGA, suggesting that the carboxyl group of CBGA is necessary for the reaction to occur.

E6 has also been shown to target other cellular proteins, thereby altering several metabolic pathways. One such target is NFX1-91, which normally represses production of telomerase, a protein that allows cells to divide an unlimited number of times. When NFX1-91 is degraded by E6, telomerase levels increase, inactivating a major mechanism keeping cell growth in check. Additionally, E6 can act as a transcriptional cofactor—specifically, a transcription activator—when interacting with the cellular transcription factor, E2F1/DP1.

Lipoprotein lipase (LPL) () is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water-soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins (VLDL), into two free fatty acids and one monoacylglycerol molecule. It is also involved in promoting the cellular uptake of chylomicron remnants, cholesterol-rich lipoproteins, and free fatty acids. LPL requires ApoC-II as a cofactor.

XPNPEP3 belongs to a family of X-pro-aminopeptidases (EC 3.4.11.9) that utilize a metal cofactor and remove the N-terminal amino acid from peptides with a proline residue in the penultimate position. It has been found that upon tumor necrosis factor stimulation, XPNPEP3 is released from mitochondria. XPNPEP3 is a new member of the TNF-TNFR2 signaling complex and plays a role in the transduction mechanism of TNFR2 signal which activates both JNK1 and JNK2 pathways.

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g.

Thermofluor has been extensively used in drug screening campaigns. Because thermofluor detects high affinity binding sites for small molecules on proteins, it can find hits that bind to active site subsites, cofactor sites, or allosteric binding sites with equal efficacy. The method typically requires the use of screening compound concentrations at >10x the desired binding threshold. Setting 5 μM as a reasonable hit threshold consequently requires a test ligand concentration of 50 to 100 μM in the sample well.

Cis-regulatory modules can regulate their target genes over large distances. Several models have been proposed to describe the way that these modules may communicate with their target gene promoter. These include the DNA scanning model, the DNA sequence looping model and the facilitated tracking model. In the DNA scanning model, the transcription factor and cofactor complex form at the cis-regulatory module and then continues to move along the DNA sequence until it finds the target gene promoter.

Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent. It is used by all forms of cellular life. NADPH is the reduced form of NADP. NADP differs from NAD by the presence of an additional phosphate group on the 2' position of the ribose ring that carries the adenine moiety.

Ronopterin (VAS-203), also known as 4-amino- tetrahydrobiopterin (4-ABH4), an analogue of BH4 (a cofactor of NOS), is an NOS inhibitor that is under development as a neuroprotective agent for the treatment of traumatic brain injury. Other NOS inhibitors that have been or are being researched for possible clinical use include cindunistat, A-84643, ONO-1714, L-NOARG, NCX-456, VAS-2381, GW-273629, NXN-462, CKD-712, KD-7040, and guanidinoethyldisulfide, among others.

WC-1 and WC-2 are bound together to form the White Collar Complex (WCC) in cultures maintained in both light or dark. Of the two proteins, it is WC-1 that actually perceives light. WC-1 is a photoreceptor that binds flavin adenine dinucleotide (FAD) as a cofactor in a specialized PAS domain known as a LOV domain. FAD absorbs blue light and initiates the conformational change in WC-1 that leads to the organism's response to light.

It must therefore be synthesized inside the brain to perform its neuronal activity. L-Phenylalanine is converted into L-tyrosine by the enzyme phenylalanine hydroxylase, with molecular oxygen (O2) and tetrahydrobiopterin as cofactors. L-Tyrosine is converted into L-DOPA by the enzyme tyrosine hydroxylase, with tetrahydrobiopterin, O2, and iron (Fe2+) as cofactors. L-DOPA is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase (also known as DOPA decarboxylase), with pyridoxal phosphate as the cofactor.

Glutamate 2,3-aminomutase () is an enzyme that belongs to the radical s-adenosyl methionine (SAM) superfamily. Radical SAM enzymes facilitate the reductive cleavage of S-adenosylmethionine (SAM) through the use of radical chemistry and an iron-sulfur cluster. This enzyme family is implicated in the biosynthesis of DNA precursors, vitamin, cofactor, antibiotic and herbicides and in biodegradation pathways. In particular, glutamate 2,3 aminomutase is involved in the conversion of L-alpha-glutamate to L-beta-glutamate in Clostridium difficile.

The final non-oxidative step of the pathway is a transketolase reaction. A transketolase utilizes a thiamine pyrophosphate, or TPP cofactor, to break the unfavorable bond between the carbon in a carbonyl and the alpha carbon. TPP attacks a xylulose 5-phosphate molecule and facilitates the cleavage of the bond between the C2 (carbonyl carbon) and the C3 (alpha carbon), where glyceraldehyde 3-phosphate is released. Then, C2 can attack erythrose 4-phosphate, which forms fructose 6-phosphate.

At the center would be the helical ribonucleocapsid, which would consist of the genomic RNA wrapped around a polymer of nucleoproteins (NP). Associated with the ribonucleoprotein would be the RNA-dependent RNA polymerase (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein would be embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles would be surrounded by a lipid membrane derived from the host cell membrane.

Without this enzyme, sulfatides build up in many tissues of the body, eventually destroying the myelin sheath of the nervous system. The myelin sheath is a fatty covering that protects nerve fibers. Without it, the nerves in the brain (central nervous system – CNS) and the peripheral nerves (peripheral nervous system – PNS) which control, among other things the muscles related to mobility, cease to function properly. Arylsulfatase A is activated by saposin B (Sap B), a non-enzymatic proteinaceous cofactor.

The venture investors in Crossmedia Services were Trident Capital, Gabriel Venture Partners and River Cites Capital. In 2006, adjustments were made to ownership: Gannett Company (42.5%), Tribune Company (42.5%), The McClatchy Company (15%). On July 8, 2008 Gannett acquired both Tribune's 42.5 percent share for $22.3 million and McClatchy's 15 percent share for $7.9 million, making ShopLocal 100 percent owned by Gannett. Shoplocal is now part of TEGNA Digital, and has merged with PointRoll to create Cofactor Digital.

Mechanism for ADP-ribosylation, with residues of the catalyzing enzyme shown in blue. The source of ADP-ribose for most enzymes that perform this modification is the redox cofactor NAD+. In this transfer reaction, the N-glycosidic bond of NAD+ that bridges the ADP- ribose molecule and the nicotinamide group is cleaved, followed by nucleophilic attack by the target amino acid side chain. ADP- ribosyltransferases can perform two types of modifications: mono-ADP ribosylation and poly-ADP ribosylation.

In enzymology, a dihydrouracil oxidase () is an enzyme that catalyzes the chemical reaction :5,6-dihydrouracil + O2 \rightleftharpoons uracil + H2O2 Thus, the two substrates of this enzyme are 5,6-dihydrouracil and O2, whereas its two products are uracil and H2O2. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with oxygen as acceptor. The systematic name of this enzyme class is 5,6-dihydrouracil:oxygen oxidoreductase. It employs one cofactor, FMN.

Metal ions are required in order for DAHP synthase to catalyze reactions. In DAHP synthase, it has been shown that binding site contains patterns of cysteine and histidine residues bound to metal ions in a Cys-X-X-His fashion. It has been shown that, in general, DAHP synthases require a bivalent metal ion cofactor in order for the enzyme to function properly. Metal ions that can function as cofactors include Mn2+, Fe2+, Co2+, Zn2+, Cu2+, and Ca2+.

Sulfite oxidase () is an enzyme in the mitochondria of all eukaryotes, with exception of the yeasts. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP in oxidative phosphorylation. This is the last step in the metabolism of sulfur-containing compounds and the sulfate is excreted. Sulfite oxidase is a metallo-enzyme that utilizes a molybdopterin cofactor and a heme group (in a case of animals).

It has been the perfect cure in this case. The active component responsible for the tumoricidal activity was found in 2000 and found to be a complex of alpha- lactalbumin and oleic acid. Endogenous human alpha-lactalbumin is complexed with a calcium ion and serves as a cofactor in lactose synthesis, but has no tumoricidal properties. The alpha-lactalbumin must be partially unfolded to allow for release of the calcium ion and replacement with an oleic acid molecule.

Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in the metabolism of every cell of the human body. It is one of eight B vitamins. It is a cofactor in DNA synthesis, and in both fatty acid and amino acid metabolism. It is particularly important in the normal functioning of the nervous system via its role in the synthesis of myelin, and in the maturation of developing red blood cells in the bone marrow.

In enzymology, a L-lysine 6-transaminase () is an enzyme that catalyzes the chemical reaction :L-lysine + 2-oxoglutarate \rightleftharpoons 2-aminoadipate 6-semialdehyde + L-glutamate Thus, the two substrates of this enzyme are L-lysine and 2-oxoglutarate, whereas its two products are 2-aminoadipate 6-semialdehyde and L-glutamate. This enzyme belongs to the family of transferases, specifically the transaminases, which transfer nitrogenous groups. This enzyme participates in lysine biosynthesis. It employs one cofactor, pyridoxal phosphate.

Small tungsten clusters have also been shown to follow an alternating pathway for nitrogen fixation. The vanadium nitrogenase releases hydrazine, an intermediate specific to the alternating mechanism. However, the lack of characterized intermediates in the native enzyme itself means that neither pathway has been definitively proven. Furthermore, computational studies have been found to support both sides, depending on whether the reaction site is assumed to be at Mo (distal) or at Fe (alternating) in the MoFe cofactor.

The MoFe protein can be replaced by alternative nitrogenases in environments low in the Mo cofactor. Two types of such nitrogenases are known: the vanadium-iron (VFe; Vnf) type and the iron-iron (FeFe; Anf) type. Both form an assembly of two α subunits, two β subunits, and two δ (sometimes γ) subunits. The delta subunits are homologous to each other, and the alpha and beta subunits themselves are homologous to the ones found in MoFe nitrogenase.

Sketch of manganese peroxidase mechanism showing the initial state, iron peroxide complex, and Compounds I and II. Here, the heme cofactor is represented via an iron-nitrogen complex. The Fe(IV) oxo-porphyrin radical resonates throughout the heme. MnP catalysis occurs in a series of irreversible oxidation-reduction (redox) reactions which follow a ping-pong mechanism with second order kinetics. In the first step of the catalytic cycle, H2O2, or an organic peroxide, enters the active site of MnP.

A number of rare metabolic disorders exist in which an individual's metabolism of biotin is abnormal, such as deficiency in the holocarboxylase synthetase enzyme which covalently links biotin onto the carboxylase, where the biotin acts as a cofactor. Biotin is composed of a ureido ring fused with a tetrahydrothiophene ring. The ureido ring acts as the carbon dioxide carrier in carboxylation reactions. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring.

It is an important intermediate in the citric acid cycle, where it is synthesized from α-ketoglutarate by α-ketoglutarate dehydrogenase through decarboxylation. During the process, coenzyme A is added. With B12 as an enzymatic cofactor, it is also synthesized from propionyl CoA, the odd-numbered fatty acid, which cannot undergo beta- oxidation. Propionyl-CoA is carboxylated to D-methylmalonyl-CoA, isomerized to L-methylmalonyl-CoA, and rearranged to yield succinyl-CoA via a vitamin B12-dependent enzyme.

PGAM2 is one of two PGAM subunits found in humans and is predominantly expressed in adult muscle. Both isozymes of PGAM are glycolytic enzymes that catalyze the reversible conversion of 3-PGA to 2-PGA using 2,3-bisphosphoglycerate as a cofactor. Since both 3-PGA and 2-PGA are allosteric regulators of the pentose phosphate pathway (PPP) and glycine and serine synthesis pathways, respectively, PGAM2 may contribute to the biosynthesis of amino acids, 5-carbon sugar, and nucleotides precursors.

To replace AdhE2, the researchers found that NADP-dependent alcohol dehydrogenase (YqhD) from E. coli to be effective for the pathway. Furthermore, the researchers needed a dehydrogenase to replace the aldehyde dehydrogenase capacity of AdhE2. CoA-acylating butyraldehyde dehydrogenase (Bldh) from C. saccharoperbutylacetonicum was found to be a good suit. Together, PhaB, Bldh, YqhD can replace Hbd and AdhE2, respectively, to change the cofactor preference of 3-ketobutyryl-CoA reduction from using NADH to using NADPH.

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co- activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g.

A 3D representation of the TPP riboswitch with thiamine bound Complex thiamine biosynthesis occurs in bacteria, some protozoans, plants, and fungi. The thiazole and pyrimidine moieties are biosynthesized separately and then combined to form thiamine monophosphate (ThMP) by the action of thiamine-phosphate synthase (EC2.5.1.3). The biosynthetic pathways may differ among organisms. In E. coli and other enterobacteriaceae, ThMP may be phosphorylated to the cofactor thiamine diphospate (ThDP) by a thiamine-phosphate kinase (ThMP + ATP → ThDP + ADP, EC 2.7.4.16).

Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms cell. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.

RPE65 has been isolated from a wide range of vertebrates including zebra fish, chicken, mice, frogs, and humans. Its structure is highly conserved between species, particularly in the beta-propeller and likely membrane bound regions. The amino acid sequences of human and bovine RPE65 differ by less than 1%. The histidine residues of the beta-propeller structure and the bound iron(II) cofactor are 100% conserved across studied RPE65 orthologs and other members of the carotenoid oxygenase family.

Additionally, while both NADH and NADPH are adequate cofactors for the reaction, NADH is preferred. The Km of the reaction is four-times smaller with NADH and the Kcat/Km is three-times greater, indicating a more efficient reaction. Homoserine dehydrogenase also exhibits multi-order kinetics at subsaturating levels of substrate. Additionally, the variable kinetics for homoserine dehydrogenase is an artifact of the faster dissociation of the amino acid substrate from the enzyme complex as compared to cofactor dissociation.

In the yeast strain Pichia pastoris, lysyl oxidase constitutes a homodimeric structure. Each monomer consists of an active site that includes a Cu(II) atom coordinated with three histidine residues as well as 2,4,5-trihydroxyphenalanine quinone (TPQ), a crucial cofactor. In humans, the LOX gene is located on chromosome 5 q23.3-31.2. The DNA sequence encodes a polypeptide of 417 amino acids, the first 21 residues of which constitute a signal peptide, with a weight of approximately 32 kDa.

Recently it has been shown that upregulation of IFRD1 in vivo in injured muscle potentiates muscle regeneration by increasing the production of staminal muscle cells (satellite cells). The underlying molecular mechanism lies in the ability of IFRD1 to cooperate with MyoD at inducing the transcriptional activity of MEF2C. This relies on the ability of IFRD1 to bind selectively MEF2C, thus inhibiting its interaction with HDAC4. Therefore, IFRD1 appears to act as a positive cofactor of MyoD.

Mitochondrial amidoxime-reducing component 1 (also known as MOCO sulphurase C-terminal domain containing 1, MOSC1 or MARC1) is an enzyme which in humans is encoded by the MOSC1 gene. MOCO stands for molybdenum cofactor. MOSC1 has been reported to reduce amidoximes to amidines. Genetic variation in MARC1 has been reported to be associated with lower blood cholesterol levels, blood liver enzyme levels, reduced liver fat and protection from cirrhosis suggesting that MARC1 deficiency may protect against liver disease.

Under ER stress, the carboxyl-terminus region of derlin-1 captures specific misfolded proteins in the ER lumen. Derlin-1 also interacts with VIMP, an ER membrane protein that recruits the cytosolic ATPase p97 and its cofactor. The interaction of derlin-1 with p97 via VIMP is essential for export of misfolded proteins. p97 is required for the transport of the misfolded proteins through the ER membrane and back to the cytosolic side for their degradation.

After acquiring his Master's Degree in Neuroscience, Mr. Armstrong spent nine years in the Genome Center at Washington University's Technology Development Group. David Messina is the Chief Operating Officer of Cofactor Genomics. He has spent the last 19 years in computational biology and genetics. He worked on the Human Genome Project at Washington University in Saint Louis, trained in molecular biology and human genetics at the University of Chicago, and earned his PhD in computational biology in Stockholm, Sweden.

In molecular biology, the Cofactor transferase family is a family of protein domains that includes biotin protein ligases, lipoate-protein ligases A, octanoyl-(acyl carrier protein):protein N-octanoyltransferases, and lipoyl- protein:protein N-lipoyltransferases. The metabolism of the cofactors Biotin and lipoic acid share this family. They also share the target modification domain (), and the sulfur insertion enzyme (). Biotin protein ligase (BPL) is the enzyme responsible for attaching biotin to a specific lysine at the biotin carboxyl carrier protein.

Relative to the abundance of molybdenum in the ocean, the amount required as a metal cofactor for enzymes in marine phytoplankton is negligible. Trace metals with nutrient-type distributions are strongly associated with the internal cycles of particulate organic matter, especially the assimilation by plankton. The lowest dissolved concentrations of these metals are at the surface of the ocean, where they are assimilated by plankton. As dissolution and decomposition occur at greater depths, concentrations of these trace metals increase.

OMIM - gamma-glutamyl carboxylase, contributed by McKusick VA, last updated October 2004 The carboxylase requires vitamin K as a cofactor and performs the reaction in a processive manner. γ-carboxyglutamate binds calcium, which is essential for its activity. For example, in prothrombin, calcium binding allows the protein to associate with the plasma membrane in platelets, bringing it into close proximity with the proteins that cleave prothrombin to active thrombin after injury.Berg JM, Tymoczko JL, Stryer L. Biochemistry, 5th ed.

Molecule 2 is transformed into molecule 3 by tautomerizing to its keto form and then being transaminated by EvaB using L-Glu as the ammonia source and PLP as a cofactor. :Vancosamine biosynth part 1 EvaC then methylates molecule 3 at the 3-C to form molecule 4 by deprotonating to form an enolate intermediate, which then attacks a SAM methyl group in the active site of EvaC. EvaD then epimerizes molecule 4 at 5-C to form molecule 5.

This amino acid is structurally related to ornithine (it is the 5-oxa derivative) and is a potent insecticide. Tobacco hornworm larvae fed a diet containing 2.5 mM canaline showed massive developmental aberrations, and most larvae so treated died at the pupal stage. It also exhibits potent neurotoxic effects in the moth. Its toxicity stems primarily from the fact that it readily forms oximes with keto acids and aldehydes, especially the pyridoxal phosphate cofactor of many vitamin B6-dependent enzymes.

The flavin-containing monooxygenase (FMO) protein family specializes in the oxidation of xeno-substrates in order to facilitate the excretion of these compounds from living organisms. These enzymes can oxidize a wide array of heteroatoms, particularly soft nucleophiles, such as amines, sulfides, and phosphites. This reaction requires an oxygen, an NADPH cofactor, and an FAD prosthetic group. FMOs share several structural features, such as a NADPH binding domain, FAD binding domain, and a conserved arginine residue present in the active site.

Pentavalent arsenic tends to be reduced to trivalent arsenic and trivalent arsenic tends to proceed via oxidative methylation in which the trivalent arsenic is made into mono, di and trimethylated products by methyltransferases and an S-adenosyl-methionine methyl donating cofactor. However, newer studies indicate that trimethylarsine has a low toxicity, and could therefore not account for the death and the severe health problems observed in the 19th century. Arsenic is not only toxic, but it also has carcinogenic effects.

These isoforms are not able to be determined from one another based on factors influencing activity. This variety also results from macro-heterogeneity, as some isoforms bind FAD at their N-terminus while others are unable to bind FAD. It is understood that this is the case because the N-terminal fold is a region known to bind FAD as a needed cofactor. Also curious is that FAD plays no observed role in active site oxidation-reduction reactions of this enzyme.

In the biosynthesis of \gamma- carboxyglutamic acid, the \gamma-proton on glutamic acid is abstracted, and CO2 is subsequently added. The reaction intermediate is a \gamma-glutamyl carbanion. This reaction is catalyzed by a carboxylase that requires vitamin K as its cofactor. It is not exactly known how vitamin K participates, but it is hypothesized that a free cysteine residue in the carboxylase converts vitamin K into an active strong base that in turn abstracts a hydrogen from glutamic acid's \gamma-carbon.

Even so, it is of tremendous commercial and societal importance. By providing challenging synthetic targets, for example, it has played a central role in the development of the field of organic chemistry. Prior to the development of analytical chemistry methods in the twentieth century, the structures of natural products were affirmed by total synthesis (so-called "structure proof by synthesis"). Early efforts in natural products synthesis targeted complex substances such as cobalamin (vitamin B12), an essential cofactor in cellular metabolism.

Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones. CYP enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses.

Iron is a necessary cofactor for many enzymes, and can act as a catalyst in the electron transport system. A. fumigatus has two mechanisms for the uptake of iron, reductive iron acquisition and siderophore-mediated. Reductive iron acquisition includes conversion of iron from the ferric (Fe+3) to the ferrous (Fe+2) state and subsequent uptake via FtrA, an iron permease. Targeted mutation of the ftrA gene did not induce a decrease in virulence in the murine model of A. fumigatus invasion.

Mm cpn (Methanococcus maripaludis chaperonin), found in the archaea Methanococcus maripaludis, is composed of sixteen identical subunits (eight per ring). It has been shown to fold the mitochondrial protein rhodanese; however, no natural substrates have yet been identified. Group II chaperonins are not thought to utilize a GroES- type cofactor to fold their substrates. They instead contain a "built-in" lid that closes in an ATP-dependent manner to encapsulate its substrates, a process that is required for optimal protein folding activity.

Bassoon protein and pLG72, are the current known proteins to physically interact and modulate human DAAO. plG72 is the product of the primate-specific G72 gene, and higher levels of both were observed in schizophrenia patients. Interaction of plG72 with hDAAO was observed to cause a time-dependent inactivation with the oxidase. This is believed to be caused by plG72 binding limiting the amount of the enzyme that is catalytically competent, and can be negated by the cofactor or any active- site ligands.

The energy input that is required for SNARE-mediated fusion to take place comes from SNARE-complex disassembly. The suspected energy source is N-ethylmaleimide-sensitive factor (NSF), an ATPase that is involved with membrane fusion. NSF homohexamers, along with the NSF cofactor α-SNAP, bind and dissociate the SNARE complex by coupling the process with ATP hydrolysis. This process allows for reuptake of synaptobrevin for further use in vesicles, whereas the other SNARE proteins remain associated with the cell membrane.

The cause of the condition is an inactivating PH mutation in either the EVER1 or EVER2 genes, which are located adjacent to one another on chromosome 17. These genes play a role in regulating the distribution of zinc in the cell nuclei. Zinc is a necessary cofactor for many viral proteins, and the activity of EVER1/EVER2 complex appears to restrict the access of viral proteins to cellular zinc stores, limiting their growth. Other genes have also rarely been associated with this condition.

As an example, the structure of C-phycocyanin from Synechococcus vulcanus has been refined to 1.6 Angstrom resolution. The (αβ) monomer consists of 332 amino acids and 3 thio-linked phycocyanobilin (PCB) cofactor molecules. Both the α- and β-subunits have a PCB at amino acid 84, but the β-subunit has an additional PCB at position 155 as well. This additional PCB faces the exterior of the trimeric ring and is therefore implicated in inter-rod energy transfer in the phycobilisome complex.

Prof Alan Battersby lecturing on porphyrin biosynthesis. Alan Battersby is, above all, known for his research on the biosynthesis of the "pigments of life" that are built on closely related tetrapyrrolic structural frameworks. His research group elucidated, in particular, the essential role played by two enzymes, deaminase and cosynthetase, in the steps from aminolevulinic acid via porphobilinogen and hydroxymethylbilane to uroporphyrinogen III. The latter is the first macrocyclic intermediate in the biosynthesis of haem, chlorophyll, vitamin B12 (cobalamin), sirohaem and cofactor F430.

The first evidence for the requirement of flavin as an enzyme cofactor came in 1935. Hugo Theorell and coworkers showed that a bright-yellow-coloured yeast protein, identified previously as essential for cellular respiration, could be separated into apoprotein and a bright-yellow pigment. Neither apoprotein nor pigment alone could catalyse the oxidation of NADH, but mixing of the two restored the enzyme activity. However, replacing the isolated pigment with riboflavin did not restore enzyme activity, despite their being indistinguishable under spectroscopy.

Mitochondrial and many bacterial SQRs are composed of four structurally different subunits: two hydrophilic and two hydrophobic. The first two subunits, a flavoprotein (SdhA) and an iron-sulfur protein (SdhB), form a hydrophilic head where enzymatic activity of the complex takes place. SdhA contains a covalently attached flavin adenine dinucleotide (FAD) cofactor and the succinate binding site and SdhB contains three iron-sulfur clusters: [2Fe-2S], [4Fe-4S], and [3Fe-4S]. The second two subunits are hydrophobic membrane anchor subunits, SdhC and SdhD.

Although the functionality of the heme in succinate dehydrogenase is still being researched, some studies have asserted that the first electron delivered to ubiquinone via [3Fe-4S] may tunnel back and forth between the heme and the ubiquinone intermediate. In this way, the heme cofactor acts as an electron sink. Its role is to prevent the interaction of the intermediate with molecular oxygen to produce reactive oxygen species (ROS). The heme group, relative to ubiquinone, is shown in image 4.

Another example is thiamine pyrophosphate (TPP), which is tightly bound in transketolase or pyruvate decarboxylase, while it is less tightly bound in pyruvate dehydrogenase. Other coenzymes, flavin adenine dinucleotide (FAD), biotin, and lipoamide, for instance, are tightly bound. Tightly bound cofactors are, in general, regenerated during the same reaction cycle, while loosely bound cofactors can be regenerated in a subsequent reaction catalyzed by a different enzyme. In the latter case, the cofactor can also be considered a substrate or cosubstrate.

In a number of enzymes, the moiety that acts as a cofactor is formed by post-translational modification of a part of the protein sequence. This often replaces the need for an external binding factor, such as a metal ion, for protein function. Potential modifications could be oxidation of aromatic residues, binding between residues, cleavage or ring- forming. These alterations are distinct from other post-translation protein modifications, such as phosphorylation, methylation, or glycosylation in that the amino acids typically acquire new functions.

The formation of oxygen radicals in the brain is achieved through the nitric oxide synthase (NOS) pathway. This reaction occurs as a response to an increase in the Ca2+ concentration inside a brain cell. This interaction between the Ca2+ and NOS results in the formation of the cofactor tetrahydrobiopterin (BH4), which then moves from the plasma membrane into the cytoplasm. As a final step, NOS is dephosphorylated yielding nitric oxide (NO), which accumulates in the brain, increasing its oxidative stress.

Beta-hexosaminidase subunit beta is an enzyme that in humans is encoded by the HEXB gene. Hexosaminidase B is the beta subunit of the lysosomal enzyme beta- hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta- hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases.

The hydrolysis of GM2-ganglioside requires three proteins. Two of them are subunits of hexosaminidase A; the third is a small glycolipid transport protein, the GM2 activator protein (GM2A), which acts as a substrate-specific cofactor for the enzyme. Deficiency in any one of these proteins leads to ganglioside storage, primarily in the lysosomes of neurons. Tay–Sachs disease (along with AB-variant GM2-gangliosidosis and Sandhoff disease) occurs because a mutation inherited from both parents deactivates or inhibits this process.

SAM-IV riboswitches are a kind of riboswitch that specifically binds S-adenosylmethionine (SAM), a cofactor used in many methylation reactions. Originally identified by bioinformatics, SAM-IV riboswitches are largely confined to the Actinomycetales, an order of Bacteria. Conserved features of SAM-IV riboswitch and experiments imply that they probably share a similar SAM-binding site to another class of SAM-binding riboswitches called SAM-I riboswitches. However, the scaffolds of these two types of riboswitch appear to be quite distinct.

The microbe theory's proponents argue that it would better explain the rapid, but continual, rise of carbon isotope level in period sediment deposits than volcanic eruption, which causes a spike in carbon levels followed by a slow decline. The microbe theory suggests that volcanic activity played a different role - supplying the nickel which Methanosarcina required as a cofactor. Thus, the microbe theory holds that Siberian volcanic activity was a catalyst for, but not the primary cause of the mass extinction.

The systematic name of this enzyme class is linoleoyl-CoA,hydrogen- donor:oxygen oxidoreductase. Other names in common use include Delta6-desaturase (D6D or Δ-6-desaturase, termed 6 after omega-6 fatty acids), Delta6-fatty acyl-CoA desaturase, Delta6-acyl CoA desaturase, fatty acid Delta6-desaturase, fatty acid 6-desaturase, linoleate desaturase, linoleic desaturase, linoleic acid desaturase, linoleoyl CoA desaturase, linoleoyl- coenzyme A desaturase, and long-chain fatty acid Delta6-desaturase. This enzyme participates in linoleic acid metabolism. It employs one cofactor, iron.

Copper amine oxidases catalyze the oxidative conversion of amines to aldehydes and ammonia in the presence of copper and quinone cofactor. This gene shows high sequence similarity to copper amine oxidases from various species ranging from bacteria to mammals. The protein contains several conserved motifs including the active site of amine oxidases and the histidine residues that likely bind copper. It may be a critical modulator of signal transmission in retina, possibly by degrading the biogenic amines dopamine, histamine, and putrescine.

In enzymology, a serine C-palmitoyltransferase () is an enzyme that catalyzes the chemical reaction: :palmitoyl-CoA + L-serine \rightleftharpoons CoA + 3-dehydro-D-sphinganine + CO2 Thus, the two substrates of this enzyme are palmitoyl-CoA and L-serine, whereas its 3 products are CoA, 3-dehydro-D- sphinganine, and CO2. This reaction is a key step in the biosynthesis of sphingosine which is a precursor of many other sphingolipids. This enzyme participates in sphingolipid metabolism. It employs one cofactor, pyridoxal phosphate.

Glycine decarboxylase () is an enzyme that catalyzes the following chemical reaction: :glycine + H-protein-lipoyllysine \rightleftharpoons H-protein-S-aminomethyldihydrolipoyllysine + CO2 Thus, the two substrates of this enzyme are glycine and H-protein-lipoyllysine, whereas its two products are H-protein-S-aminomethyldihydrolipoyllysine and CO2. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with a disulfide as acceptor. This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, pyridoxal phosphate.

In enzymology, a hyponitrite reductase is an enzyme that catalyzes the oxidation of hydroxylamine by the nicotinamide adenine dinucleotide cation (NAD+) into hyponitrous acid HON=NOH: :2 + 2 NAD+ \rightleftharpoons HON=NOH + 2 NADH + 2 H+ This systematic name of this enzyme class hydroxylamine:NAD+ oxidoreductase. It is also called NADH2:hyponitrite oxidoreductase. This enzyme belongs to the family of oxidoreductases, specifically those acting on other nitrogenous compounds as donors with NAD+ or NADP+ as acceptor. It employs one cofactor, metal.

308x308px The mechanism of this enzyme is stepwise and steady-state random. Specifically, the catalytic reaction begins with the NADPH and the substrate attaching to the binding site of the enzyme, followed by the protonation and the hydride transfer from the cofactor NADPH to the substrate. However, two latter steps do not take place simultaneously in a same transition state. In a study using computational and experimental approaches, Liu et al conclude that the protonation step precedes the hydride transfer.

The copper amine oxidase 3-dimensional structure was determined through X-ray crystallography. The copper amine oxidases occur as mushroom-shaped homodimers of 70-95 kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis.

In enzymology, a ferredoxin-NADP reductase () abbreviated FNR, is an enzyme that catalyzes the chemical reaction :2 reduced ferredoxin + NADP + H \rightleftharpoons 2 oxidized ferredoxin + NADPH The 3 substrates of this enzyme are reduced ferredoxin, NADP, and H, whereas its two products are oxidized ferredoxin and NADPH. It has a flavin cofactor, FAD. This enzyme belongs to the family of oxidoreductases, that use iron-sulfur proteins as electron donors and NAD or NADP as electron acceptors. This enzyme participates in photosynthesis.

In enzymology, a 2,5-dihydroxypyridine 5,6-dioxygenase () is an enzyme that catalyzes the chemical reaction :2,5-dihydroxypyridine + O2 \rightleftharpoons N-formylmaleamic acid The 2 substrates of this enzyme are 2,5-dihydroxypyridine and O2, whereas its product is N-formylmaleamic acid. This enzyme belongs to the family of oxidoreductases, specifically those acting on single donors with O2 as oxidant and incorporation of two atoms of oxygen into the substrate (oxygenases). The oxygen incorporated need not be derived from O2. It employs one cofactor, iron.

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes [e.g.

In vitro, this behaviour catalyzes the general formation of DNA polymers without specific length. The 2-15nt DNA fragments produced in vivo are hypothesized to act in signaling pathways related to DNA repair and/or recombination machinery. Like many polymerases, TdT requires a divalent cation cofactor, however, TdT is unique in its ability to use a broader range of cations such as Mg2+, Mn2+, Zn2+ and Co2+. The rate of enzymatic activity depends on the available divalent cations and the nucleotide being added.

Thus, when GlcN6P levels are high, the glmS ribozyme is activated and the mRNA transcript is degraded but in the absence of GlcN6P the gene continues to be translated into glutamine-fructose-6-phosphate amidotransferase and GlcN6P is produced. GlcN6P is a cofactor for this cleavage reaction, as it directly participates as an acid-base catalyst. This RNA is the first riboswitch also found to be a self-cleaving ribozyme and, like many others, was discovered using a bioinformatics approach.

The treatment for this disease is similar to treatment of other fatty acid oxidation disorders, by trying to restore biochemical and physiologic homeostasis, by promoting anabolism and providing alternative sources of energy. Flavin adenine dinucleotide supplementation has also been identified as a therapy for this deficiency, because it is an essential cofactor for proper function of SCAD. SCAD deficiency is inherited in an autosomal recessive manner. Carrier testing can be performed for at-risk family members, and prenatal testing is also a possibility.

The RP2 locus has been implicated as one cause of X-linked retinitis pigmentosa. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of beta-tubulin folding. Progressive retinal degeneration may therefore be due to the accumulation of incorrectly-folded photoreceptor or neuron-specific tubulin isoforms, followed by progressive cell death. The RP2 protein is also involved in regulating the function and extension of the outer segment of cone photoreceptors in mice.

ALDH3A1 bound to NAD+ ALDH3A1 is a homodimer consisting of alpha helices (43.8%), beta sheets (4.2%), p-loop turns (28.2%) and random coils (23.8%). The catalytic residue–Cys244—is located on an active site that contains a Rossmann fold that binds the enzyme's cofactor, NAD(P)+. ALDH3A1's catalytic mechanism mirrors that of other enzymes of the aldehyde dehydrogenase family. The sulfur atom of Cys244 attacks the carbonyl of the aldehyde substrate in a nucleophilic attack that releases a hydride ion.

Computing methods have been used to design a protein with a novel fold, named Top7, and sensors for unnatural molecules. The engineering of fusion proteins has yielded rilonacept, a pharmaceutical that has secured Food and Drug Administration (FDA) approval for treating cryopyrin-associated periodic syndrome. Another computing method, IPRO, successfully engineered the switching of cofactor specificity of Candida boidinii xylose reductase. Iterative Protein Redesign and Optimization (IPRO) redesigns proteins to increase or give specificity to native or novel substrates and cofactors.

By modifying the types of cofactors used and the times at which they are used, the outcome of the metabolic network can change. To create a greater production of a product, metabolic engineers have the ability to supply the network with whichever cofactor is best suited for that specific process. This leads to the optimization of networks to give a higher production of desired products. Also, changing the cofactors used in a network may be an ingenious solution to a complicated problem.

As a whole, this is called a protein's quaternary structure. The quaternary structure is generated by the formation of relatively strong non-covalent interactions, such as hydrogen bonds, between different subunits to generate a functional polymeric enzyme. Some proteins also utilize non-covalent interactions to bind cofactors in the active site during catalysis, however a cofactor can also be covalently attached to an enzyme. Cofactors can be either organic or inorganic molecules which assist in the catalytic mechanism of the active enzyme.

At pH 7 GAK allows Hsc70 to uncoat clathrin baskets and at pH 6 Hsc70 binds clathrin baskets without uncoating clathrin. Without taking into account GAK’s kinase domain, GAK is 43% identical to auxilin, a neuronal cell uncoating clathrin cofactor, in its amino acid composition. GAK is 57% homologous to auxilin if conserved residues are included in the comparison. Though similar domains of these two molecules suggest and have similar functions, the proteins carry these functions out in different manners.

However, in some we find a monomer ("which is more active and efficient [than its dimer counterpart"). The structure of ACS has been largely determined via X-ray crystallography. Conservation of the residues in ACS's catalytic domain and sequence homology suggest that ACS catalyzes the synthesis of ACC in a similar fashion as other enzymes that require PLP as a cofactor. However, unlike many other PLP- dependent enzymes, Lys (278) is not the only residue that interacts with the substrate.

Ascorbate and ascorbic acid are both naturally present in the body, since the forms interconvert according to pH. Oxidized forms of the molecule such as dehydroascorbic acid are converted back to ascorbic acid by reducing agents. Vitamin C functions as a cofactor in many enzymatic reactions in animals (including humans) that mediate a variety of essential biological functions, including wound healing and collagen synthesis. In humans, vitamin C deficiency leads to impaired collagen synthesis, contributing to the more severe symptoms of scurvy.

Ascorbic acid efflux by embryo of dicots plants is a well-established mechanism of iron reduction, and a step obligatory for iron uptake. All plants synthesize ascorbic acid. Ascorbic acid functions as a cofactor for enzymes involved in photosynthesis, synthesis of plant hormones, as an antioxidant and also regenerator of other antioxidants. Plants use multiple pathways to synthesize vitamin C. The major pathway starts with glucose, fructose or mannose (all simple sugars) and proceeds to L-galactose, L-galactonolactone and ascorbic acid.

11-cis-retinol dehydrogenase is also mainly associated to the smooth endoplasmic reticulum of RPE cells. The 32-kDa integral membrane protein protein (p32) was found to act as the stereospecific 11-cis-retinol dehydrogenase in the presence of NAD+ cofactor, and p32 catalyzes the biosynthesis of 11-cis retinal commonly found visual chromophore. One of the widely studied genes of retinol dehydrogenase RDH12, which encodes retinol dehydrogenase is part of the superfamily of short- chained alcohol dehydrogenases and reductases.

The reaction catalyzed by methionine synthase (click to enlarge) Methionine synthase catalyzes the final step in the regeneration of methionine(Met) from homocysteine(Hcy). The overall reaction transforms 5-methyltetrahydrofolate(N5-MeTHF) into tetrahydrofolate (THF) while transferring a methyl group to Homocysteine to form Methionine. Methionine synthase is the only mammalian enzyme that metabolizes N5-MeTHF to regenerate the active cofactor THF. In cobalamin-dependent forms of the enzyme, the reaction proceeds by two steps in a ping-pong reaction.

The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle. Phenylalanine dehydrogenase (PheDH) is an NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate. Valine dehydrogenase (ValDH) is an NADP- dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate. These enzymes contain two domains, an N-terminal dimerisation domain, and a C-terminal domain.

Recently, TIM-1 has been shown to be a receptor or cofactor for Ebola virus entry. TIM-1 binds to Ebola virus glycoproteins (GP) and mediates Ebola virus cellular entry by increasing Ebola virus infectivity in cell lines with a low susceptibility. Moreover, reducing expression of endogenous TIM-1 in highly permissive cell lines decreased Ebola virus infectivity. Furthermore, TIM-1 IgV domain specific antibody ARD5 inhibited Ebola virus infectivity, indicating that TIM-1 was critical for Ebola virus entry.

In regards to the mechanism of protein S deficiency, Protein S is made in liver cells and the Endothelium. Protein S is a cofactor of APC both work to degrade factor V and factor VIII. It has been suggested that Zn2+ might be necessary for Protein S binding to factor Xa. Mutations in this condition change amino acids, which in turn disrupts blood clotting. Functional protein S is lacking, which normally turns off clotting proteins, this increases risk of blood clots.

During her postdoctoral studies, she shows that germline cells require a specific stimulation to acquire DNA methylation, via the cofactor 3 DNMT3L. Déborah Bourch'his runs a research team studying epigenetic decisions and reproduction in the department 'Genetics and Developmental biology' of the Curie Institute.. Her research focuses on understanding the regulation of epigenetic information within the peri-conception window, from Gametogenesis to early embryonic development. She has published several key publications in the field. Her work has been awarded several prestigious prizes.

Overexposure to essential metals can also have detrimental consequences on the epigenome. For example, when manganese, a metal normally used by the body as a cofactor, is present at high concentrations in the blood it can negatively affect the central nervous system. Studies have shown that accumulation of manganese leads to dopaminergic cell death and consequently plays a role in the onset of Parkinson's disease (PD). A hallmark of Parkinson's disease is the accumulation of α-Synuclein in the brain.

Gephyrin, an integral membrane protein believed to coordinate glycine receptors, is coded by the gene GPHN. A heterozygous mutation in this gene has been identified in a sporadic case of hyperekplexia, though experimental data is inconclusive as to whether the mutation is pathogenic. Gephyrin is essential for glycine receptor clustering at synaptic junctions through its action of binding both the glycine receptor beta subunit and internal cellular microtubule structures. Gephyrin also assists in clustering GABA receptors at synpases and molybdenum cofactor synthesis.

When an action potential occurs in a cell, the electrical signal reaches the presynaptic terminal and the depolarization causes calcium channels to open, releasing calcium to travel down its electrochemical gradient. This influx of calcium subsequently is what causes the neurotransmitter vesicles to fuse with the presynaptic membrane. The calcium ions initiate the interaction of obligatory cofactor proteins with SNARE proteins to form a SNARE complex. These SNARE complexes mediate vesicle fusion by pulling the membranes together, leaking the neurotransmitters into the synaptic cleft.

This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.

The human body can employ cyanide-like umpolung reactivity without having to rely on the toxic cyanide ion. Thiamine (which itself is an N-heterocyclic carbene) pyrophosphate (TPP) serves a functionally identical role. The thiazolium ring in TPP is deprotonated within the hydrophobic core of the enzyme, resulting in a carbene which is capable of umpolung. Deprotonation of thiazole moiety in thiamine pyrophosphate results in ambivalent chemical reactivity Enzymes which use TPP as a cofactor can catalyze umpolung reactivity, such as the decarboxylation of pyruvate.

In [NiFe] and [FeFe] hydrogenases, electrons travel through a series of metallorganic clusters that comprise a long distance; the active site structures remain unchanged during the whole process. In [Fe]-only hydrogenases, however, electrons are directly delivered to the active site via a short distance. Methenyl-H4MPT+, a cofactor, directly accepts the hydride from H2 in the process. [Fe]-only hydrogenase is also known as H2-forming methylenetetrahydromethanopterin (methylene-H4MPT) dehydrogenase, because its function is the reversible reduction of methenyl-H4MPT+ to methylene-H4MPT.

Cryptochromes (CRY1, CRY2) are evolutionarily old and highly conserved proteins that belong to the flavoproteins superfamily that exists in all kingdoms of life. All members of this superfamily have the characteristics of an N-terminal photolyase homology (PHR) domain. The PHR domain can bind to the flavin adenine dinucleotide (FAD) cofactor and a light-harvesting chromophore. Cryptochromes are derived from and closely related to photolyases, which are bacterial enzymes that are activated by light and involved in the repair of UV-induced DNA damage.

Pirin is a protein that in humans is encoded by the PIR gene. This gene encodes a member of the cupin superfamily. The encoded protein is an Fe(II)-containing nuclear protein expressed in all tissues of the body and concentrated within dot-like subnuclear structures. Interactions with nuclear factor I/CCAAT box transcription factor as well as B cell lymphoma 3-encoded oncoprotein suggest the encoded protein may act as a transcriptional cofactor and be involved in the regulation of DNA transcription and replication.

In fact, if is a divisor of such that , then is a divisor of such that . If one tests the values of in increasing order, the first divisor that is found is necessarily a prime number, and the cofactor cannot have any divisor smaller than . For getting the complete factorization, it suffices thus to continue the algorithm by searching a divisor of that is not smaller than and not greater than . There is no need to test all values of for applying the method.

Biotin synthase (BioB) () is an enzyme that catalyzes the conversion of dethiobiotin (DTB) to biotin; this is the final step in the biotin biosynthetic pathway. Biotin, also known as vitamin B7, is a cofactor used in carboxylation, decarboxylation, and transcarboxylation reactions in many organisms including humans. Biotin synthase is an S-Adenosylmethionine (SAM) dependent enzyme that employs a radical mechanism to thiolate dethiobiotin, thus converting it to biotin. This radical SAM enzyme belongs to the family of transferases, specifically the sulfurtransferases, which transfer sulfur- containing groups.

In the monooxygenases, only a single atom of dioxygen is incorporated into a substrate with the other being reduced to a water molecule. The dioxygenases () catalyze the oxidation of a substrate without the reduction of one oxygen atom from dioxygen into a water molecule. However, this definition is ambiguous because it does not take into account how many substrates are involved in the reaction. The majority of dioxygenases fully incorporate dioxygen into a single substrate, and a variety of cofactor schemes are utilized to achieve this.

The mechanism of arginine decarboxylase is analogous to other deaminating and decarboxylating PLP enzymes in its use of a Schiff base intermediate. Initially, Lys386 residue is displaced in a transamination reaction by the L-arginine substate, forming an arginine Schiff base with the PLP cofactor. Decarboxylation of arginine carboxylate group then occurs, where it is hypothesized that the C-C bond broken is perpendicular to the PLP pyridine ring. The pyridine nitrogen group acts as an electron-withdrawing group that facilitates the C-C bond breaking.

It employs one cofactor, thiamin diphosphate (TPP), and plays a key role in catabolism of oxalate, a highly toxic compound that is a product of the oxidation of carbohydrates in many bacteria and plants. Oxalyl-CoA decarboxylase is extremely important for the elimination of ingested oxalates found in human foodstuffs like coffee, tea, and chocolate, and the ingestion of such foods in the absence of Oxalobacter formigenes in the gut can result in kidney disease or even death as a result of oxalate poisoning.

GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. It has a similar pathology to Sandhoff disease and Tay–Sachs disease. The three diseases are classified together as the GM2 gangliosidoses, because each disease represents a distinct molecular point of failure in the activation of the same enzyme, beta-hexosaminidase. AB variant is caused by a failure in the gene that makes an enzyme cofactor for beta-hexosaminidase, called the GM2 activator.

Mediator of RNA polymerase II transcription subunit 7 is an enzyme that in humans is encoded by the MED7 gene. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1.

Hole-modified BH GalNac-Ts paired with UDP-GalNac analogs to tag GalNac T substrates to be visualized with click chemistry. The N-Acetylgalactosaminyl transferase (GalNac Ts) family transfers N-Acetylgalactosamine to the Ser/Thr side chains (O-linked glycosylation) of its substrates, using UDP-GalNac as a cofactor. Like kinases, substrate profiling for specific isoforms of GalNac Ts has been difficult to achieve. The absence of a glycosylation consensus sequence and the variability of glycan elaboration pose a challenge to studying O-GalNac glycoproteins.

Mediator of RNA polymerase II transcription subunit 17 is an enzyme that in humans is encoded by the MED17 gene. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1.

Catsup regulates production of dopamine by serving as a negative regulator of rate-limiting enzymes in dopamine and pteridine synthesis pathways, both of which are required to occur for production of dopamine. In dopamine synthesis pathway, Catsup negatively regulates Tyrosine hydroxylase (TH) activity, preventing TH catalyzed conversion of tyrosine to the precursor of dopamine, L-Dopa. In pteridine biosynthesis pathway, Catsup negatively regulates the activity of GTP Cyclohydrolase I (GTPCH), preventing GTPCH catalyzed biosynthesis of TH cofactor required for TH catalytic activity and regulation, tetrahydrobiopterin (BH4).

Antibodies against Esa1p specifically immunoprecipitate NuA4 activity whereas the complex purified from a temperature-sensitive esa1 mutant loses its acetyltransferase activity at the restrictive temperature. Additionally, another subunit of the complex has been identified as the product of TRA1, an ATM-related essential gene homologous to human TRRAP, an essential cofactor for c-Myc- and E2F-mediated oncogenic transformation. Finally, the ability of NuA4 to stimulate GAL4–VP16-driven transcription from chromatin templates in vitro is also lost in the temperature-sensitive esa1 mutant.

The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles. Its enzyme function has been determined as a ketimine reductase, reducing cyclic ketimines to their reduced forms. Either NADH or NADPH can be used as cofactor. The most active substrate at pH 5.0 is aminoethylcysteine ketimine (AECK), however at neutral pH (pH 7.2) the most active substrate is 1-piperideine-2-carboxylate which is an important part of the pipecolic acid pathway.

Zinc is the only cofactor necessary for activity. The substrate, adenosine, is stabilized and bound to the active site by nine hydrogen bonds. The carboxyl group of Glu217, roughly coplanar with the substrate purine ring, is in position to form a hydrogen bond with N1 of the substrate. The carboxyl group of Asp296, also coplanar with the substrate purine ring, forms hydrogen bond with N7 of the substrate. The NH group of Gly184 is in position to form a hydrogen bond with N3 of the substrate.

Given the C3 is constantly being turned over in the alternative pathway and its ability to rapidly amplify a signal, these proteins are important in regulating the temporal and spatial effects of C3b to infected tissues. An example RCA is membrane cofactor protein (MCP; CD46), which is ubiquitously expressed and plays a critical role in protecting host cells from damage by the C3b. Furthermore, host cells express p33 (globular C1q receptor) on the surface, which binds C1q, and prevents it from initiating complement activation.

During B12 deficiency, this reaction cannot proceed, which leads to the accumulation of 5-methyltetrahydrofolate. This accumulation depletes the other types of folate required for purine and thymidylate synthesis, which are required for the synthesis of DNA. Inhibition of DNA replication in maturing red blood cells results in the formation of large, fragile megaloblastic erythrocytes. The neurological aspects of the disease are thought to arise from the accumulation of methylmalonyl CoA due to the requirement of B12 as a cofactor to the enzyme methylmalonyl CoA mutase.

This gene encodes one subunit of the 2-oxoglutarate dehydrogenase complex. This complex catalyzes the overall conversion of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO2 during the citric acid cycle. The protein is located in the mitochondrial matrix and uses thiamine pyrophosphate as a cofactor. The overall complex furthers catalysis by keeping the necessary substrates for the reaction close within the enzyme, thus creating a situation in which it is more likely that the substrate will be in the favorable conformation and orientation.

The active site of the aldehyde dehydrogenase enzyme is largely conserved throughout the different classes of the enzyme and, although the number of amino acids present in a subunit can change, the overall function of the site changes little. The active site binds to one molecule of an aldehyde and one of either NAD+ or NADP+ that functions as a cofactor. A cysteine and a glutamate will interact with the aldehyde substrate. Many other residues will interact with the NAD(P)+ to hold it in place.

Early chemosynthetic organisms likely produced methane, an important trap for molecular oxygen, since methane readily oxidizes to carbon dioxide (CO2) and water in the presence of UV radiation. Modern methanogens require nickel as an enzyme cofactor. As the Earth's crust cooled and the supply of volcanic nickel dwindled, oxygen-producing algae began to out- perform methane producers, and the oxygen percentage of the atmosphere steadily increased. From 2.7 to 2.4 billion years ago, the rate of deposition of nickel declined steadily from a level 400 times today's.

450px Pyruvate decarboxylation requires a few cofactors in addition to the enzymes that make up the complex. The first is thiamine pyrophosphate (TPP), which is used by pyruvate dehydrogenase to oxidize pyruvate and to form a hydroxyethyl- TPP intermediate. This intermediate is taken up by dihydrolipoyl transacetylase and reacted with a second lipoamide cofactor to generate an acetyl-dihydrolipoyl intermediate, releasing TPP in the process. This second intermediate can then be attacked by the nucleophilic sulfur attached to Coenzyme A, and the dihydrolipoamide is released.

Cofactors can be divided into two major groups: organic cofactors, such as flavin or heme; and inorganic cofactors, such as the metal ions Mg2+, Cu+, Mn2+ and iron-sulfur clusters. Organic cofactors are sometimes further divided into coenzymes and prosthetic groups. The term coenzyme refers specifically to enzymes and, as such, to the functional properties of a protein. On the other hand, "prosthetic group" emphasizes the nature of the binding of a cofactor to a protein (tight or covalent) and, thus, refers to a structural property.

In enzymology, a trans-cinnamate 4-monooxygenase () is an enzyme that catalyzes the chemical reaction :trans-cinnamate + NADPH + H+ \+ O2 \rightleftharpoons 4-hydroxycinnamate + NADP+ \+ H2O The 4 substrates of this enzyme are trans-cinnamate, NADPH, H+, and O2, whereas its 3 products are 4-hydroxycinnamate, NADP+, and H2O. This enzyme participates in phenylalanine metabolism and phenylpropanoid biosynthesis. It employs one cofactor, heme. This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen.

Deficiencies of vitamins B6, B9 and B12 can lead to high homocysteine levels. Vitamin B12 acts as a cofactor for the enzyme methionine synthase (which forms part of the S-adenosylmethionine (SAM) biosynthesis and regeneration cycle). Vitamin B12 deficiency prevents the 5-methyltetrahydrofolate (5-MTHF) form of folate from being converted into THF due to the "methyl trap". This disrupts the folate pathway and leads to an increase in homocysteine which damages cells (for example, damage to endothelial cells can result in increased risk of thrombosis).

Covalent catalysis involves the substrate forming a transient covalent bond with residues in the enzyme active site or with a cofactor. This adds an additional covalent intermediate to the reaction, and helps to reduce the energy of later transition states of the reaction. The covalent bond must, at a later stage in the reaction, be broken to regenerate the enzyme. This mechanism is utilised by the catalytic triad of enzymes such as proteases like chymotrypsin and trypsin, where an acyl-enzyme intermediate is formed.

Vitamin B12 adenosylcobalamin in mitochondrion—cholesterol and protein metabolism The enzymes that use as a built-in cofactor are methylmalonyl-CoA mutase (PDB 4REQ) and methionine synthase (PDB 1Q8J). The metabolism of propionyl-CoA occurs in the mitochondria and requires Vitamin (as adenosylcobalamin) to make succinyl-CoA. When the conversion of propionyl- CoA to succinyl-CoA in the mitochondria fails due to Vitamin deficiency, elevated blood levels of methylmalonic acid (MMA) occur. Thus, elevated blood levels of homocysteine and MMA may both be indicators of vitamin deficiency.

This function of IKK-α has been shown to be independent of the protein's kinase activity and of the NF-κB pathway. Instead it is thought that IKK-α regulates skin differentiation by acting as a cofactor in the TGF-β / Smad2/3 signaling pathway. The zebrafish homolog of IKK-α has also been shown to play a role in the differentiation of the embryonic epithelium. Zebrafish embryos born from mothers that are mutant in IKK-α do not produce a differentiated outer epithelial monolayer.

In enzymology, a dimethylglycine oxidase () is an enzyme that catalyzes the chemical reaction :N,N-dimethylglycine + H2O + O2 \rightleftharpoons sarcosine + formaldehyde + H2O2 The 3 substrates of this enzyme are N,N-dimethylglycine, H2O, and O2, whereas its 3 products are sarcosine, formaldehyde, and H2O2. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with oxygen as acceptor. The systematic name of this enzyme class is N,N-dimethylglycine:oxygen oxidoreductase (demethylating). It employs one cofactor, FAD.

While GCDH deficiency is a rare disease, GLO deficiency is the most common of metabolic diseases affecting children, limiting ascorbic acid biosynthesis to a minute fraction of what other non-primate species synthesize. It was thus called by OMIM (Online Mendeleian Inheritance in Man) a "public" error of metabolism. Ascorbic acid (Vitamin C) is a necessary cofactor for the utilization of lysine in collagen synthesis. Collagen, the most abundant protein in the human body, requires great amounts of lysine, the most abundant amino acids in proteins.

In bacteria, trans-translation, a highly conserved mechanism, acts as a direct counter to the accumulation of non-stop RNA, inducing decay and liberating the misregulated ribosome. Originally discovered in Escherichia coli, the process of trans-translation is made possible by the interactions between transfer-messenger RNA (tmRNA) and the cofactor protein SmpB, which allows for the stable binding of the tmRNA to the stalled ribosome.Karzai, A. Wali; Roche, Eric D.; Sauer, Robert T.; (2000). “The SsrA–SmpB system for protein tagging, directed degradation and ribosome rescue”.

Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1.

Some examples of inorganic cofactors are iron or magnesium, and some examples of organic cofactors include ATP or coenzyme A. Organic cofactors are more specifically known as coenzymes, and many enzymes require the addition of coenzymes to assume normal catalytic function in a metabolic reaction. The coenzymes bind to the active site of an enzyme to promote catalysis. By engineering cofactors and coenzymes, a naturally occurring metabolic reaction can be manipulated to optimize the output of a metabolic network. Common cofactor NADH, the first discovered.

PAL active sitePhenylalanine ammonia lyase is composed of four identical subunits composed mainly of alpha-helices, with pairs of monomers forming a single active site. Catalysis in PAL may be governed by the dipole moments of seven different alpha helices associated with the active site. The active site contains the electrophilic group MIO non-covalently bonded to three helices. Leu266, Asn270, Val269, Leu215, Lys486, and Ile472 are located on the active site helices, while Phe413, Glu496, and Gln500 contribute to the stabilization of the MIO cofactor.

Threonine ammonia-lyase, also commonly referred to as threonine deaminase or threonine dehydratase, is an enzyme responsible for catalyzing the conversion of L-threonine into alpha-ketobutyrate and ammonia. Alpha-ketobutyrate can be converted into L-isoleucine, so threonine ammonia-lyase functions as a key enzyme in BCAA synthesis. It employs a pyridoxal-5'-phosphate cofactor, similar to many enzymes involved in amino acid metabolism. It is found in bacteria, yeast, and plants, though most research to date has focused on forms of the enzyme in bacteria.

While both forms of aconitases have similar functions, most studies focus on ACO2. The iron-sulfur (4Fe-4S) cofactor is held in place by the sulfur atoms on Cys385, Cys448, and Cys451, which are bind to three of the four available iron atoms. A fourth iron atom is included in the cluster together with a water molecule when the enzyme is activated. This fourth iron atom binds to either one, two, or three partners; in this reaction, oxygen atoms belonging to outside metabolites are always involved.

Figure 2: The mechanism for the conversion of Glyoxylate and NAD(P)H to Glycolate and NAD(P)+ The enzyme catalyzes the transfer of a hydride from NAD(P)H to glyoxylate, causing a reduction of the substrate to glycolate and an oxidation of the cofactor to NAD(P)+. Figure 2 shows the mechanism for this reaction. It is thought that the two residues Glu270 and His288 are important for the enzyme's catalytic function, while the residue Arg241 is thought to be important for substrate specificity.

At least one member (YebN of E. coli, TC# 2.A.107.1.1) has been shown to function as a putative manganese efflux pump. Manganese sensitivity and intracellular manganese levels significantly increased in bacteria when the mntP (formerly yebN) gene, which encodes the MntP efflux pump, was deleted. While manganese is a highly important trace nutrient for organisms from bacteria to humans, acting as an important element in the defense against oxidative stress and as an enzyme cofactor, it becomes toxic when present in excess.

Choline kinase (also known as CK, ChoK and choline phosphokinase) is an enzyme which catalyzes the first reaction in the choline pathway for phosphatidylcholine (PC) biosynthesis. This reaction involves the transfer of a phosphate group from adenosine triphosphate (ATP) to choline in order to form phosphocholine. :ATP + choline \rightleftharpoons ADP + O-phosphocholine Thus, the two substrates of this enzyme are ATP and choline, whereas its two products are adenosine diphosphate (ADP) and O-phosphocholine. Choline kinase requires magnesium ions (+2) as a cofactor for this reaction.

Choline kinase catalyzes the formation of phoshocholine, the committed step in phosphatidylcholine biosynthesis. Phosphatidylcholine is the major phospholipid in eukaryotic membranes. Phosphatidylcholine is important for a variety of function in eukaryotes such as facilitating the transport of cholesterol through the organism, acting as a substrate for the production of second messengers and as a cofactor for the activity of several membrane- related enzymes. CK also plays a vital role in the production of sphingomyelin, another important membrane phospholipid and in the regulation of cell growth.

The phylogeny of S. muelleri has been discovered to follow the phylogeny of the Hemiptera clade, Auchenorrhyncha. The first association between S. muelleri and Auchenorrhyncha is estimated to have occurred sometime between 260–280 million years ago. Further evidence supports the idea that S. muelleri has coevolved with another symbiotic lineage from the taxonomic class Betaproteobacteria. The result of this coevolution can be noticed through the fact that both S. muelleri and its host leave cofactor and vitamin production to another member of the symbiotic relationship.

NSFL1 cofactor p47 is a protein that in humans is encoded by the NSFL1C gene. N-ethylmaleimide-sensitive factor (NSF) and valosin-containing protein (p97) are two ATPases known to be involved in transport vesicle/target membrane fusion and fusions between membrane compartments. A trimer of the protein encoded by this gene binds a hexamer of cytosolic p97 and is required for p97-mediated regrowth of Golgi cisternae from mitotic Golgi fragments. Multiple transcript variants encoding several different isoforms have been found for this gene.

Nucleoporin 50 (Nup50) is a protein that in humans is encoded by the NUP50 gene. The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins that functions as a soluble cofactor in importin-alpha:beta-mediated nuclear protein import.

FTR is unique among thioredoxin reductases because it uses an Fe-S cluster cofactor rather than flavoproteins to reduce disulfide bonds. FTR catalysis begins with its interaction with reduced Ferredoxin. This proceeds with the attraction between FTR Lys-47 and Ferredoxin Glu-92. One electron from Ferredoxin and one electron from the Fe-S center is abstracted to break FTR's Cys-87 and Cys-57 disulfide bond, create a nucleophilic Cys-57, and oxidize the Fe-S center from [4Fe-4S]2+ to [4Fe-4S]3+.

Senior dogs require a larger amount of riboflavin for maintenance compared to adult dogs. Vitamin B2, also known as riboflavin, plays an important role as a cofactor for the metabolism of carbohydrates. Riboflavin is required in the diet to prevent cracking and dry skin, as well as a darkening of the pigmentation of skin. Riboflavin is also important for the vision of the senior dog as deficiencies can cause alterations in blood supply to the cornea which may lead to impaired vision and potential blindness.

These genes are sufficient for assembly of the BMC since they can be transplanted from one type of bacterium to another, resulting in a functional metabolosome in the recipient. This is an example of bioengineering that likewise provides evidence in support of the selfish operon hypothesis. 1,2-propanediol is dehydrated to propionaldehyde by propanediol dehydratase, which requires vitamin B12 as a cofactor. Propionaldehyde causes DNA mutations and as a result is toxic to cells, possibly explaining why this compound is sequestered within a BMC.

Seegers was, at the time, searching for vitamin K-dependent coagulation factors undetected by clotting assays, which measure global clotting function. Soon after this, Seegers recognised Stenflo's discovery was identical with his own. Activated protein C was discovered later that year, and in 1977 it was first recognised that APC inactivates Factor Va. In 1980, Vehar and Davie discovered that APC also inactivates Factor VIIIa, and soon after, Protein S was recognised as a cofactor by Walker. In 1982, a family study by Griffin et al.

Fibrinogen is a dimeric glycoprotein, which contains two pairs of Aα-, Bβ- peptide chains and y- chains. There are two isoforms of this fibrinogen, one with two yA-chains (yA/yA) and one with a yA-chain and a y’-chain (yA,y’) When fibrinogen is cleaved by thrombin, it releases fibrinopeptide A or B. Thrombin acts on two exosites to fibrinogen. Exosite 1 mediates the binding of thrombin to the Aα- and Bβ-chains, and exosite 2 causes an interaction with a second fibrinogen molecule at the C-terminus of the y’-chain. Consequently, when thrombin binds a yA/yA fibinogen only exosite 1 is occupied, and when it binds yA/y’ both exosites are bound tightly. So fibrinogen yA/y’ is a competitor to yA/yA, which decrease the amount of clotting. yA/y’ binds with a factor 20-fold greater than yA/yA. There are also clotting inhibitors like antithrombin and heparin cofactor II, which prevent clotting when it isn’t necessary. In contrast, batroxobin isn’t inhibited by antithrombin and heparin cofactor II. Batroxobin also has a high Kd value for binding both forms yA/yA and yA/y’.

Once the 5-FU or 5-FUdR prodrugs have been bioactivated resulting in FdUMP, they will already be recognized by the TS enzyme. When this happens, the enzyme goes through a conformational change to enable the union of the cofactor 5,10-Methylenetetrahydrofolic (5,10-CH2THF), which is necessary for the operation of the enzyme. Once this compound is united, the inhibition reaction begins with a different mechanism that would take place with the uracil. The reaction begins when a cysteine residue present at the active enzyme site attacks the pyrimidine in position 2.

One of acamprosate's mechanisms of action is the enhancement of GABA signaling at GABAA receptors via positive allosteric receptor modulation. It has been purported to open the chloride ion channel in a novel way as it does not require GABA as a cofactor, making it less liable for dependence than benzodiazepines. Acamprosate has been successfully used to control tinnitus, hyperacusis, ear pain and inner ear pressure during alcohol use due to spasms of the tensor tympani muscle. In addition, alcohol also inhibits the activity of N-methyl-D-aspartate receptors (NMDARs).

The DNA ligase IV complex, consisting of the catalytic subunit DNA ligase IV and its cofactor XRCC4 (Dnl4 and Lif1 in yeast), performs the ligation step of repair. XLF, also known as Cernunnos, is homologous to yeast Nej1 and is also required for NHEJ. While the precise role of XLF is unknown, it interacts with the XRCC4/DNA ligase IV complex and likely participates in the ligation step. Recent evidence suggests that XLF promotes re-adenylation of DNA ligase IV after ligation, recharging the ligase and allowing it to catalyze a second ligation.

Industrially, molybdenum compounds (about 14% of world production of the element) are used in high-pressure and high-temperature applications as pigments and catalysts. are by far the most common bacterial catalysts for breaking the chemical bond in atmospheric molecular nitrogen in the process of biological nitrogen fixation. At least 50 molybdenum enzymes are now known in bacteria, plants, and animals, although only bacterial and cyanobacterial enzymes are involved in nitrogen fixation. These nitrogenases contain an iron-molybdenum cofactor FeMoco, which is believed to contain either Mo(III) or Mo(IV).

Ferulic acid decarboxylase (Fdc1) from A. niger co-expressed in E.coli with UbiX from E.coli (AnFdc1UbiX) once purified had clear spectral differences to singly expressed AnFdc1, and was capable of in vitro decarboxylation of a range of aromatic carboxylic acids. The atomic resolution of the crystal structure of AnFdc1UbiX, allowed elucidation of the structure of the modified FMN cofactor classified as prFMN (Figure 2). The crystal structure revealed an isopentenyl-adduct to the N5-C6 of FMN, with the modifications branched nature and the position of the covalent linkages with flavin suggesting prenylation. Figure 2.

The B domain C-terminus acts as a cofactor for the anticoagulant protein C activation by protein S. Activation of factor V to factor Va is done by cleavage and release of the B domain, after which the protein no longer assists in activating protein C. The protein is now divided to a heavy chain, consisting of the A1-A2 domains, and a light chain, consisting of the A3-C1-C2 domains. Both form non-covalently a complex in a calcium-dependent manner. This complex is the pro-coagulant factor Va.

The thereby activated factor V (now called FVa) is a cofactor of the prothrombinase complex: The activated factor X (FXa) enzyme requires calcium and activated factor V (FVa) to convert prothrombin to thrombin on the cell surface membrane. Factor Va is degraded by activated protein C, one of the principal physiological inhibitors of coagulation. In the presence of thrombomodulin, thrombin acts to decrease clotting by activating protein C; therefore, the concentration and action of protein C are important determinants in the negative feedback loop through which thrombin limits its own activation.

Adenylyl cyclase is a 12-transmembrane glycoprotein that catalyzes ATP to form cAMP with the help of cofactor Mg2+ or Mn2+. The cAMP produced is a second messenger in cellular metabolism and is an allosteric activator of protein kinase A. Protein kinase A is an important enzyme in cell metabolism due to its ability to regulate cell metabolism by phosphorylating specific committed enzymes in the metabolic pathway. It can also regulate specific gene expression, cellular secretion, and membrane permeability. The protein enzyme contains two catalytic subunits and two regulatory subunits.

Cytochrome d, previously known as cytochrome a2, is a name for all cytochromes (electron-transporting heme proteins) that contain heme D as a cofactor. Two unrelated classes of cytochrome d are known: Cytochrome bd, an enzyme that generates a charge across the membrane so that protons will move, and cytochrome cd1 (NirS; SCOP ), a nitrite reductase. Cytochrome bd is found in plenty of aerobic bacteria, especially when it has grown with a limited oxygen supply. Compared to other terminal oxidases, it is notable for its high oxygen affinity and resistance to cyanide poisoning.

Biotin synthase is not found in humans. Since biotin is an important cofactor for many enzymes, humans must consume biotin through their diet from microbial and plant sources. However, the human gut microbiome has been shown to contain Escherichia coli that do contain biotin synthase, providing another source of biotin for catalytic use. The amount of E. coli that produce biotin is significantly higher in adults than in babies, indicating that the gut microbiome and developmental stage should be taken into account when assessing a person's nutritional needs.

While iron is by far the most prevalent cofactor used for enzymatic dioxygenation, it is not required by all dioxygenases for catalysis. Quercetin 2,3-dioxygenase (quercetinase, QueD) catalyzes the dioxygenolytic cleavage of quercetin to 2-protocatechuoylphloroglucinolcarboxylic acid and carbon monoxide. The most characterized enzyme, from Aspergillus japonicus, requires the presence of copper, and bacterial quercetinases have been discovered that are quite promiscuous (cambialistic) in their requirements of a metal center, with varying degrees of activity reported with substitution of divalent manganese, cobalt, iron, nickel and copper. (Quercetin, role in metabolism).

The conversion of phytoene to lycopene in plants and cyanobacteria (left) compared to bacteria and fungi(right). PDS converts 15-cis-phytoene into 9,15,9'-tri-cis-ζ-carotene through reduction of the enzymes non-covalently bound FAD cofactor. This conversion introduces two additional double bonds at positions 11 and 11' of the carbon chain and isomerizes two adjacent already existing double bonds at positions 9 and 9' from trans to cis. The electrons involved in the reaction are subsequently transferred onto plastoquinone and to plastid terminal oxidase PTOX ultimately coupling the desaturation to oxygen reduction.

The FBXL3 protein plays a role in the negative feedback loop of the mammalian molecular circadian rhythm. The PER and CRY proteins inhibit the transcription factors CLOCK and BMAL1. The degradation of PER and CRY prevent the inhibition of the CLOCK and BMAL1 protein heterodimer. In the nucleus, the FBXL3 protein targets CRY1 and CRY2 for polyubiquitination, which triggers the degradation of the proteins by the proteasome. FBXL3 binds to CRY2 by occupying its flavin adenine dinucleotide (FAD) cofactor pocket with a C-terminal tail and buries the PER- binding interface on the CRY2 protein.

Generated from 2VYC. In E. coli arginine decarboxylase, each homodimer has two active sites that are buried about 30 Å from the dimer surface. The active site, found in the PLP-binding domain, consists of the PLP cofactor bound to a lysine residue in the form of a Schiff base. The phosphate group of PLP is held in place through hydrogen bonding with the alcoholic side chains of several serine and threonine residues, as well as through hydrogen bonding with the imidazole side chain of a histidine residue.

First, it has been widely reported since the 1960s that hyperglycemia causes an increase in the flux through aldose reductase and the polyol pathway. Increased activity of the detoxifying aldose reductase enzyme leads to a depletion of the essential cofactor NADH, thereby disrupting crucial cell processes. Second, increasing fructose 6-phosphate, a glycolysis intermediate, will lead to increased flux through the hexosamine pathway. This produces N-acetyl glucosamine that can add on serine and threonine residues and alter signaling pathways as well as cause pathological induction of certain transcription factors.

Both enzymes require cofactors: COMT uses Mg2+ as a cofactor while MAO uses FAD. The first step of the catabolic process is mediated by either MAO or COMT which depends on the tissue and location of catecholamines (for example degradation of catecholamines in the synaptic cleft is mediated by COMT because MAO is a mitochondrial enzyme). The next catabolic steps in the pathway involve alcohol dehydrogenase, aldehyde dehydrogenase and aldehyde reductase. The end product of epinephrine and norepinephrine is vanillylmandelic acid (VMA) which is excreted in the urine.

In higher plants, linalool, is an acyclic monoterpenoid. Like the majority of monoterpenes, it starts at the condensation of dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) to form geranyl pyrophosphate (GPP). With the aid of linalool synthase (LIS), water attacks to form the chiral center.LIS appears to show a limonene synthase-type catalysis through a simplified "metal-cofactor-binding domain [where the majority] of the residues involved in substrate...binding [are] in the C-terminal part of the protein" suggesting stereoselectivity and the reasoning behind why some plants have varying levels of each enantiomer.

Activated mTORC1 will phosphorylate translation inhibitor 4E-BP1, releasing it from eukaryotic translation initiation factor 4E (eIF4E). eIF4E is now free to join the eukaryotic translation initiation factor 4G (eIF4G) and the eukaryotic translation initiation factor 4A (eIF4A). This complex then binds to the 5' cap of mRNA and will recruit the helicase eukaryotic translation initiation factor A (eIF4A) and its cofactor eukaryotic translation initiation factor 4B (eIF4B). The helicase is required to remove hairpin loops that arise in the 5' untranslated regions of mRNA, which prevent premature translation of proteins.

This is how the protein checks for the recognition site as it allows the DNA duplex to follow the shape of the protein. In other words, recognition happens through indirect readout of the structural parameters of the DNA, rather than via specific base sequence recognition. Each MetJ dimer contains two binding sites for the cofactor S-Adenosyl methionine (SAM) which is a product in the biosynthesis of methionine. When SAM is present, it binds to the MetJ protein, increasing its affinity for its cognate operator site, which halts transcription of genes involved in methionine synthesis.

Some amino acids contain the opposite absolute chirality, chemicals that are not available from normal ribosomal translation/transcription machinery. Most bacterial cells walls are formed by peptidoglycan, a polymer composed of amino sugars crosslinked with short oligopeptides bridged between each other. The oligopeptide is non-ribosomally synthesised and contains several peculiarities including D-amino acids, generally D-alanine and D-glutamate. A further peculiarity is that the former is racemised by a PLP-binding enzymes (encoded by alr or the homologue dadX), whereas the latter is racemised by a cofactor independent enzyme (murI).

If this is not done, the glucose will rapidly consume the remaining thiamine reserves, exacerbating this condition. The observation of edema in MR, and also the finding of inflation and macrophages in necropsied tissues,James S. Nelson, Hernando Mena & S. Schochet, Principles and Practice of Neuropathology, page 193, edited University of Hawaii, has led to successful administration of antiinflammatories. Other nutritional abnormalities should also be looked for, as they may be exacerbating the disease. In particular, magnesium, a cofactor of transketolase which may induce or aggravate the disease.

UDP-N-acetylglucosamine 4,6-dehydratase (configuration-inverting) (, FlaA1, UDP-N-acetylglucosamine 5-inverting 4,6-dehydratase, PseB, UDP-N- acetylglucosamine hydro-lyase (inverting, UDP-2-acetamido-2,6-dideoxy-beta-L- arabino-hex-4-ulose-forming)) is an enzyme with systematic name UDP-N-acetyl- alpha-D-glucosamine hydro-lyase (inverting; UDP-2-acetamido-2,6-dideoxy-beta- L-arabino-hex-4-ulose-forming). This enzyme catalyses the following chemical reaction : UDP-N-acetyl-alpha-D-glucosamine \rightleftharpoons UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose + H2O This enzyme contains NADP+ as a cofactor.

Synergistic catalysts are very common in biological systems. The reactions occur by a molecule binding to a protein as a substrate and becoming active and being reacted with a coenzyme such as NADPH which is essentially an activated hydride. A specific example of this is shown by the synthesis of tetrahydrofolate via the enzyme dihydrofolate reductase. Dihydrofolate reductase catalytically activates dihydrofolate by protonating the imine, while NADPH, essentially a hydride source activated by the cofactor NADP+, can then come in and add a hydride across the imine to afford the product.

The proposed methyl transfer from a SAM-utilizing enzyme was supported by earlier feeding studies with labeled methionine; labeled methionine is used because methionine is converted into SAM within cells. Even further, this study used stereospecifically labeled methionine ([methyl-(2H-3H)]-(2S, methyl-R)-methionine) to show that methylation occurred with a net retention of stereochemistry at the methyl group. The author speculated that net retention indicated a radical mechanism with a B12 intermediate. Radical transfer with a Cobalamin B12 cofactor and SAM has been shown with the few characterized radical SAM methyltransferases.

Eflornithine is a "suicide inhibitor," irreversibly binding to ornithine decarboxylase (ODC) and preventing the natural substrate ornithine from accessing the active site (Figure 1). Within the active site of ODC, eflornithine undergoes decarboxylation with the aid of cofactor pyridoxal 5'-phosphate (PLP). Because of its additional difluoromethyl group in comparison to ornithine, eflornithine is able to bind to a neighboring Cys-360 residue, permanently remaining fixated within the active site. During the reaction, eflornithine's decarboxylation mechanism is analogous to that of ornithine in the active site, where transamination occurs with PLP followed by decarboxylation.

Chelex resin is often used for DNA extraction in preparation for polymerase chain reaction by binding to cations including Mg2+, which is an essential cofactor for DNases. Chelex protects the sample from DNases that might remain active after the boiling and could subsequently degrade the DNA, rendering it unsuitable for PCR. After boiling, the Chelex-DNA preparation is stable and can be stored at 4°C for 3–4 months. Polar resin beads bind polar cellular components after breaking open cells, while DNA and RNA remain in water solution above the Chelex resin.

Hypoglycin A is a protoxin, meaning that the molecule is not toxic in itself but is broken down into toxic products when ingested. The branched-chain alpha-keto acid dehydrogenase complex, that normally converts leucine, isoleucine, or valine into acyl-CoA derivatives, converts Hypoglycin A into highly toxic MCPA-CoA. The FAD cofactor necessary for the beta oxidation of fatty acids associates with the alpha carbon of MCPA-CoA creating an irreversible complex that disables the enzyme. In addition, MCPA-CoA blocks some enzymes that are required for gluconeogenesis.

In Archaean oceans, phosphoenolpyruvate may have been present abiotically. A simple diagram demonstrating the final step of glycolysis, the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP) by pyruvate kinase, yielding one molecule of pyruvate and one molecule of ATP.In yeast cells, the interaction of yeast pyruvate kinase (YPK) with PEP and its allosteric effector Fructose 1,6-bisphosphate (FBP,) was found to be enhanced by the presence of Mg2+. Therefore, Mg2+ was concluded to be an important cofactor in the catalysis of PEP into pyruvate by pyruvate kinase.

Two families of dioxygenases were discovered by Osamu Hayaishi and Kizo Hashimoto in 1950: catechol 1,2-dioxygenase and catechol 2,3-dioxygenase (2,3-CTD). The two enzymes were identified to be a part of two separate catechol dioxygenase families: 1,2-CTD was classified as an intradiol dioxygenase while 2,3-CTD was classified as an extradiol dioxygenase. The two enzymes can be distinguished based on their reaction products and cofactors. 1,2-CTD uses Fe3+ as a cofactor to cleave the carbon-carbon bond between the phenolic hydroxyl groups of catechol, thus yielding muconic acid as its product.

Since the RCL is still intact, the first strand of the C-sheet has to peel off to allow full RCL insertion. Regulation of the latency transition can act as a control mechanism in some serpins, such as PAI-1. Although PAI-1 is produced in the inhibitory S conformation, it "auto-inactivates" by changing to the latent state unless it is bound to the cofactor vitronectin. Similarly, antithrombin can also spontaneously convert to the latent state, as an additional modulation mechanism to its allosteric activation by heparin.

This intermediate is subsequently attacked by a second GSH to regenerate the selenol and the glutathione cofactor is released in its oxidized form, GSSG. The catalytic mechanism of GPx, involves selenol (R-SeH), selenenyl sulfide (R1-SeS-R2), and selenenic acid intermediates.H. J. Forman, J. Fukuto, M.Torres, Signal Transduction by Reactive Oxygen and Nitrogen Species: Pathways and Chemical Principles, Kluwer, 2003. :RSeH + H2O2 → RSeOH + H2O :RSeOH + GSH → GS-SeR + H2O :GS-SeR + GSH → GS-SG + RSeH In the absence of thiols, selenols tend to overoxidize to produce seleninic acids.

A strong focus of her research is to study the enzyme that is responsible for the conversion of dinitrogen (N2) to ammonia (NH3)—Nitrogenase. Serena DeBeer and her group study this remarkable system comprising a FeMo cofactor (FeMoco) as its active site, and structural model complexes utilizing high-resolution X-ray absorption (XAS) and X-ray emission spectroscopy (XES). Through this work, great progress has been made in understanding the structure of this active site. A key contribution was a spectroscopic identification of the central atom in the active site as a carbide.

A prosthetic group is the non-amino acid component that is part of the structure of the heteroproteins or conjugated proteins, being covalently linked to the apoprotein. Not to be confused with the cofactor that binds to the enzyme apoenzyme (either a holoprotein or heteroprotein) by non-covalent binding.s a non-protein (non-amino acid) This is a component of a conjugated protein that is required for the protein's biological activity. The prosthetic group may be organic (such as a vitamin, sugar, RNA, phosphate or lipid) or inorganic (such as a metal ion).

Ascorbic acid operates as an anti- oxidant and essential enzyme cofactor in the human body. In in vitro studies, the primary mechanism of high dosage intravenous ascorbic acid can be related to ascorbic acid's pro-oxidant activity, whereby hydrogen peroxide is formed. In the extracellular fluid of cells, ascorbic acid dissociates into an ascorbate radical upon the reduction of transition metal ions, such as ferric or cupric cations. These transition metal ions will then reduce dissolved oxygen into a superoxide radical- this will then react with hydrogen to form hydrogen peroxide.

This proton gradient is the driving force for ATP synthesis via photophosphorylation and coupling the absorption of light energy and photolysis of water to the creation of chemical energy during photosynthesis. The O2 remaining after oxidation of the water molecule is released into the atmosphere. Water oxidation is catalyzed by a manganese- containing enzyme complex known as the oxygen evolving complex (OEC) or water- splitting complex found associated with the lumenal side of thylakoid membranes. Manganese is an important cofactor, and calcium and chloride are also required for the reaction to occur.

The cytochrome P450 (CYP) superfamily of membrane-bound (typically endoplasmic reticulum-bound) enzymes contain a heme cofactor and therefore are hemoproteins. The superfamily comprises more than 11,000 genes categorized into 1,000 families that are distributed broadly throughout bacteria, archaea, fungi, plants, animals, and even viruses (see Cytochrome P450). The CYP enzymes metabolize an enormously large variety of small and large molecules including foreign chemical substances, i.e. xenobiotics and pharmaceuticals, as well as a diversity of endogenously formed substances such as various steroids, vitamin D, bilirubin, cholesterol, and fatty acids.

The TATA box is also found in 40% of the core promoters of genes that code for the actin cytoskeleton and contractile apparatus in cells. The type of core promoter affects the level of transcription and expression of a gene. TATA-binding protein (TBP) can be recruited in two ways, by SAGA, a cofactor for RNA polymerase II, or by TFIID. When promoters use the SAGA/TATA box complex to recruit RNA polymerase II, they are more highly regulated and display higher expression levels than promoters using the TFIID/TBP mode of recruitment.

Sorbitol dehydrogenase uses NAD+ as a cofactor; its reaction is sorbitol + NAD+ \--> fructose + NADH + H+. A zinc ion is also involved in catalysis. Organs that use it most frequently include the liver and seminal vesicle; it is found in all kinds of organisms from bacteria to humans. A secondary use is the metabolism of dietary sorbitol, though sorbitol is known not to be absorbed as well in the intestine as its related compounds glucose and fructose, and is usually found in quite small amounts in the diet (except when used as an artificial sweetener).

The principal substrate of physiologic importance of glucokinase is glucose, and the most important product is glucose-6-phosphate (G6P). The other necessary substrate, from which the phosphate is derived, is adenosine triphosphate (ATP), which is converted to adenosine diphosphate (ADP) when the phosphate is removed. The reaction catalyzed by glucokinase is: Action of glucokinase on glucose ATP participates in the reaction in a form complexed to magnesium (Mg) as a cofactor. Furthermore, under certain conditions, glucokinase, like other hexokinases, can induce phosphorylation of other hexoses (6 carbon sugars) and similar molecules.

Although the healthy body stores three to five years' worth of B12 in the liver, the usually undetected autoimmune activity in one's gut over a prolonged period of time leads to B12 depletion and the resulting anemia. B12 is required by enzymes for two reactions: the conversion of methylmalonyl CoA to succinyl CoA, and the conversion of homocysteine to methionine. In the latter reaction, the methyl group of 5-methyltetrahydrofolate is transferred to homocysteine to produce tetrahydrofolate and methionine. This reaction is catalyzed by the enzyme methionine synthase with B12 as an essential cofactor.

A rarer form of hyperphenylalaninemia is tetrahydrobiopterin deficiency, which occurs when the PAH enzyme is normal, and a defect is found in the biosynthesis or recycling of the cofactor tetrahydrobiopterin (BH4). BH4 is necessary for proper activity of the enzyme PAH, and this coenzyme can be supplemented as treatment. Those who suffer from this form of hyperphenylalaninemia may have a deficiency of tyrosine (which is created from phenylalanine by PAH), in which case treatment is supplementation of tyrosine to account for this deficiency. Levels of dopamine can be used to distinguish between these two types.

Nearly all animal life is dependent on bacteria for survival as only bacteria and some archaea possess the genes and enzymes necessary to synthesize vitamin B12, also known as cobalamin, and provide it through the food chain. Vitamin B12 is a water-soluble vitamin that is involved in the metabolism of every cell of the human body. It is a cofactor in DNA synthesis, and in both fatty acid and amino acid metabolism. It is particularly important in the normal functioning of the nervous system via its role in the synthesis of myelin.

Additionally, the primary structures are shown to be similar between mammalian SDH and microbial threonine dehydratase, especially in the sequences surrounding the PLP cofactor and the G-residues surrounding the PLP's phosphate group. Thus, in PLP enzymes, there is high conservation of the active site residues during evolution. With active site sequence conservation, it is suggested that dehydratase enzymes originated from a common ancestor. File:sequencehomologySDH.png Figure 8 shows the sequence similarities of the amino acid sequence of human SDH with those of rat SDH, and yeast and E. coli threonine dehydratases.

The cofactor is sandwiched between the side chain of Phe40 and the main chain of Ala222. Each of the polar substituents of PLP is coordinated by functional groups: the pyridinium nitrogen of PLP is hydrogen-bonded to the side chain of Cys303, the C3-hydroxyl group of PLP is hydrogen-bonded to the side chain of Asn67, and the phosphate group of PLP is coordinated by main chain amides from the tetraglycine loop. (Figure 3 and Figure 4). File:PLPbindingsitesSDH.png Figure 3 shows the hydrogen bonding in the active site of SDH.

Adenosylmethionine decarboxylase is an enzyme that catalyzes the conversion of S-adenosyl methionine to S-adenosylmethioninamine. Polyamines such as spermidine and spermine are essential for cellular growth under most conditions, being implicated in many cellular processes including DNA, RNA and protein synthesis. S-adenosylmethionine decarboxylase (AdoMetDC) plays an essential regulatory role in the polyamine biosynthetic pathway by generating the n-propylamine residue required for the synthesis of spermidine and spermine from putrescein. Unlike many amino acid decarboxylases AdoMetDC uses a covalently bound pyruvate residue as a cofactor rather than the more common pyridoxal 5'-phosphate.

In enzymology, a N-acyl-D-amino-acid deacylase () is an enzyme that catalyzes the chemical reaction :N-acyl-D-amino acid + H2O \rightleftharpoons an acid + D-amino acid Thus, the two substrates of this enzyme are N-acyl-D-amino acid and H2O, whereas its two products are acid and D-amino acid. This enzyme belongs to the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically in linear amides. The systematic name of this enzyme class is N-acyl-D-amino acid amidohydrolase. It employs one cofactor, zinc.

In enzymology, a N-acyl-D-aspartate deacylase () is an enzyme that catalyzes the chemical reaction :N-acyl-D-aspartate + H2O \rightleftharpoons a carboxylate + D-aspartate Thus, the two substrates of this enzyme are N-acyl- D-aspartate and H2O, whereas its two products are carboxylate and D-aspartate. This enzyme belongs to the family of hydrolases, those acting on carbon- nitrogen bonds other than peptide bonds, specifically in linear amides. The systematic name of this enzyme class is N-acyl-D-aspartate amidohydrolase. It employs one cofactor, zinc.

In enzymology, a N-acyl-D-glutamate deacylase () is an enzyme that catalyzes the chemical reaction :N-acyl-D-glutamate + H2O \rightleftharpoons a carboxylate + D-glutamate Thus, the two substrates of this enzyme are N-acyl- D-glutamate and H2O, whereas its two products are carboxylate and D-glutamate. This enzyme belongs to the family of hydrolases, those acting on carbon- nitrogen bonds other than peptide bonds, specifically in linear amides. The systematic name of this enzyme class is N-acyl-D-glutamate amidohydrolase. It employs one cofactor, zinc.

He distinguished two new signaling pathways for excitable cells. A fast, pertussis toxin-sensitive pathway turned on inward rectifier K+ channels and turned off Ca2+ channels by G protein Gβγ subunits. A slow, pertussis toxin- insensitive pathway turned off some K+ and Ca2+ channels by depleting the plasma membrane phosphoinositides, phosphatidylinositol 4,5-bisphosphate (PIP2). New tools and findings from the Hille lab, together with the initial finding (1996) from Donald W. Hilgemann's lab at UT southwestern, demonstrated that PIP2 is an essential cofactor for many ion channels and transporters.

This increases the functionality of the protein; unmodified amino acids are typically limited to acid-base reactions, and the alteration of resides can give the protein electrophilic sites or the ability to stabilize free radicals. Examples of cofactor production include tryptophan tryptophylquinone (TTQ), derived from two tryptophan side chains, and 4-methylidene-imidazole-5-one (MIO), derived from an Ala-Ser-Gly motif. Characterization of protein-derived cofactors is conducted using X-ray crystallography and mass spectroscopy; structural data is necessary because sequencing does not readily identify the altered sites.

The haloacid dehalogenase (HAD) superfamily is a further PP group that uses Asp as a nucleophile and was recently shown to have dual- specificity. These PPs can target both Ser and Tyr, but are thought to have greater specificity towards Tyr. A subfamily of HADs, the Eyes Absent Family (Eya), are also transcription factors and can therefore regulate their own phosphorylation and that of transcriptional cofactor/s, and contribute to the control of gene transcription. The combination of these two functions in Eya reveals a greater complexity of transcriptional gene control than previously thought .

Formation of pretetramid allows for one of the most important intermediates en route to the biosynthesis of oxytetracycline; this is the generation of anhydrotetracycline. Anhydrotetracycline contains the first functionalized A ring in this biosynthetic pathway. After the formation of anhydrotetracycline, ATC monooxygenase (OxyS) oxidizes the C-6 position in an enantioselective manner in the presence of the cofactor NADPH and atmospheric oxygen to produce 5a,11a-dehydrotetracycline. Next, a hydroxylation occurs at the C-5 position of 5a,11a-dehydrotetracycline via the oxygenase encoded as OxyE in the oxytetracycline gene cluster.

Sepiapterin, also known as 2-amino-6-[(2S)-2-hydroxypropanoyl]-7,8-dihydro-1H-pteridin-4-one, is a member of the pteridine class of organic chemicals. Sepiapterin can be metabolized into tetrahydrobiopterin via a salvage pathway. Tetrahydrobiopterin is an essential cofactor in humans for breakdown of phenylalanine and a catalyst of the metabolism of phenylalanine, tyrosine, and tryptophan to precursors of the neurotransmitters dopamine and serotonin. Deficiency of tetrahydrobiopterin can cause toxic buildup of phenylalanine (phenylketonuria) as well as deficiencies of dopamine, norepinephrine, and epinephrine, leading to dystonia and other neurological illnesses.

The substrate specificity of exosomes is improved in the presence of TRAMP complex as it acts as a crucial cofactor and helps in maintaining various activities. In this way, TRAMP plays a critical role in ridding the cell of noncoding transcripts generated through pervasive RNA polymerase II transcription, as well as functioning in the biogenesis and turnover of functional coding and noncoding RNAs. TRAMP complex also affects various other RNA processes either directly or indirectly. It is involved in RNA export, Splicing, hetero-chromatic gene silencing and helps in maintaining stability of genome.

The second stage involves the abstraction of the pro-R hydrogen atom from C-4 of the proline substrate followed by radical combination, which yields hydroxyproline. As a consequence of the reaction mechanism, one molecule of 2-oxoglutarate is decarboxylated, forming succinate. This succinate is hydrolyzed and replaced with another 2-oxoglutarate after each reaction, and it has been concluded that in the presence of 2-oxoglutarate, enzyme-bound Fe2+ is rapidly converted to Fe3+, leading to inactivation of the enzyme. Ascorbate is utilized as a cofactor to reduce Fe3+ back to Fe2+.

DHODH can vary in cofactor content, oligomeric state, subcellular localization, and membrane association. An overall sequence alignment of these DHODH variants presents two classes of DHODHs: the cytosolic Class 1 and the membrane-bound Class 2. In Class 1 DHODH, a basic cysteine residue catalyzes the oxidation reaction, whereas in Class 2, the serine serves this catalytic function. Structurally, Class 1 DHODHs can also be divided into two subclasses, one of which forms homodimers and uses fumarate as its electron acceptor, and the other which forms heterotetramers and uses NAD+ as its electron acceptor.

The substrate is held in place by several non- covalent interactions with the protein scaffold. The hydroxylase, 4-hydroxybenzoate 3-monooxygenase, proceeds through a catalytic process that begins with the entrance of NADPH and 4-hydroxybenzoate (the native substrate) into the active site of the enzyme. This results in formation of an enzyme- flavin-substrate-NADPH complex, after which the flavin cofactor, FAD, is reduced by NADPH. NADP+ is lost and O2 enters into the complex, followed by oxidation of the flavin to form a hydroperoxide, which acts as the hydroxide transfer reagent.

These assembly factors contribute to COX structure and functionality, and are involved in several essential processes, including transcription and translation of mitochondrion-encoded subunits, processing of preproteins and membrane insertion, and cofactor biosynthesis and incorporation. Currently, mutations have been identified in seven COX assembly factors: SURF1, SCO1, SCO2, COX10, COX15, COX20, COA5 and LRPPRC. Mutations in these proteins can result in altered functionality of sub-complex assembly, copper transport, or translational regulation. Each gene mutation is associated with the etiology of a specific disease, with some having implications in multiple disorders.

The systematic name of this enzyme class is O4-succinyl-L- homoserine:L-cysteine S-(3-amino-3-carboxypropyl)transferase. Other names in common use include O-succinyl-L-homoserine succinate-lyase (adding cysteine), O-succinylhomoserine (thiol)-lyase, homoserine O-transsuccinylase, O-succinylhomoserine synthase, O-succinylhomoserine synthetase, cystathionine synthase, cystathionine synthetase, homoserine transsuccinylase, 4-O-succinyl- L-homoserine:L-cysteine, and S-(3-amino-3-carboxypropyl)transferase. This enzyme participates in 4 metabolic pathways: methionine metabolism, cysteine metabolism, selenoamino acid metabolism, and sulfur metabolism. It employs one cofactor, pyridoxal phosphate.

Active site of Nickel superoxide dismutase Cofactor F430 contains nickel in a tetrapyrrole derivative, and is used in the production of methane. Some hydrogenase enzymes contain a nickel-iron cluster as an active site in which the nickel atom is held in place by cysteine or selenocysteine. Plant ureases contain a bis-μ-hydroxo dimeric nickel cluster. CO-methylating acetyl-CoA synthase contains two active nickel atoms, one is held in a square planar coordination by two cysteine and two amide groups, and the other nickel is held by three sulfur atoms.

EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2). EZH2's catalytic activity relies on its formation of a complex with at least two other PRC2 components, SUZ12 and EED. As a histone methyltransferase (HMTase), EZH2's primary function is to methylate Lys-27 on histone 3 (H3K27me) by transferring a methyl group from the cofactor S-adenosyl-L-methionine (SAM). EZH2 is capable of mono-, di-, and tri-methylation of H3K27 and has been associated with a variety of biological functions, including transcriptional regulation in hematopoiesis, development, and cell differentiation.

In enzymology, a D-arabinono-1,4-lactone oxidase () is an enzyme that catalyzes the chemical reaction :D-arabinono-1,4-lactone + O2 \rightleftharpoons D-erythro-ascorbate + H2O2 Thus, the two substrates of this enzyme are D-arabinono-1,4-lactone and O2, whereas its two products are D-erythro-ascorbate and H2O2. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with oxygen as acceptor. The systematic name of this enzyme class is D-arabinono-1,4-lactone:oxygen oxidoreductase. It employs one cofactor, FAD.

Lignin is highly resistant to biodegradation and only higher fungi and some bacteria are capable of degrading the polymer via an oxidative process. This process has been studied extensively in the past twenty years, but the mechanism has not yet been fully elucidated. Lignin is found to be degraded by enzyme lignin peroxidases produced by some fungi like Phanerochaete chrysosporium. The mechanism by which lignin peroxidase (Lip) interacts with the lignin polymer involves Veratryl alcohol (Valc); which is a secondary metabolite of white rot fungi that acts as a cofactor for the enzyme.

MnP has a globular structure containing 11-12 α-helices, depending on the species it is produced in. It is stabilized by 10 cystine amino acid residues which form 5 disulfide bridges, one of which is near the C-terminal area. The active site contains a heme cofactor which is bound by two Ca2+ ions, one above and one below the heme. Near the internal heme propionate are three acidic residues which are used to stabilize Mn(II) or Mn(III) when it is bound to the enzyme.

Succinate-Q oxidoreductase. Succinate-Q oxidoreductase, also known as complex II or succinate dehydrogenase, is a second entry point to the electron transport chain. It is unusual because it is the only enzyme that is part of both the citric acid cycle and the electron transport chain. Complex II consists of four protein subunits and contains a bound flavin adenine dinucleotide (FAD) cofactor, iron–sulfur clusters, and a heme group that does not participate in electron transfer to coenzyme Q, but is believed to be important in decreasing production of reactive oxygen species.

In enzymology, a trypanothione-disulfide reductase () is an enzyme that catalyzes the chemical reaction :trypanothione + NADP+ \rightleftharpoons trypanothione disulfide + NADPH + H+ Thus, the two substrates of this enzyme are trypanothione and NADP+, whereas its 3 products are trypanothione disulfide, NADPH, and H+. This enzyme belongs to the family of oxidoreductases, specifically those acting on a sulfur group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is trypanothione:NADP+ oxidoreductase. Other names in common use include trypanothione reductase, and NADPH2:trypanothione oxidoreductase. It employs one cofactor, FAD.

Many steps are involved, but the result is the formation of a proton gradient across the thylakoid membrane, which is used to synthesize adenosine triphosphate (ATP) via photophosphorylation.Raven 2005, 115–27 The remaining (after production of the water molecule) is released into the atmosphere.Water oxidation is catalyzed by a manganese-containing enzyme complex known as the oxygen evolving complex (OEC) or water-splitting complex found associated with the lumenal side of thylakoid membranes. Manganese is an important cofactor, and calcium and chloride are also required for the reaction to occur.

Two pathways have been proposed based on models that differ in the proximity of the iron to the pterin cofactor and the number of water molecules assumed to be iron- coordinated during catalysis. According to one model, an iron dioxygen complex is initially formed and stabilized as a resonance hybrid of Fe2+O2 and Fe3+O2−. The activated O2 then attacks BH4, forming a transition state characterized by charge separation between the electron-deficient pterin ring and the electron-rich dioxygen species. The Fe(II)-O-O-BH4 bridge is subsequently formed.

Deletion of the N-terminal domain also eliminates the lag time while increasing the affinity for Phe by nearly two-fold; no difference is observed in the Vmax or Km for the tetrahydrobiopterin cofactor. Additional regulation is provided by Ser16; phosphorylation of this residue does not alter enzyme conformation but does reduce the concentration of Phe required for allosteric activation. This N-terminal regulatory domain is not observed in bacterial PAHs but shows considerable structural homology to the regulatory domain of phosphogylcerate dehydrogenase, an enzyme in the serine biosynthetic pathway.

The prothrombinase complex consists of the serine protease, Factor Xa, and the protein cofactor, Factor Va. The complex assembles on negatively charged phospholipid membranes in the presence of calcium ions. The prothrombinase complex catalyzes the conversion of prothrombin (Factor II), an inactive zymogen, to thrombin (Factor IIa), an active serine protease. The activation of thrombin is a critical reaction in the coagulation cascade, which functions to regulate hemostasis in the body. To produce thrombin, the prothrombinase complex cleaves two peptide bonds in prothrombin, one after Arg271 and the other after Arg320.

In Factor V Leiden, a G1691A nucleotide replacement results in an R506Q amino acid mutation. Factor V Leiden increases the risk of venous thrombosis by two known mechanisms. First, activated protein C normally inactivates Factor Va by cleaving the cofactor at Arg306, Arg506, and Arg679. The Factor V Leiden mutation at Arg506 renders Factor Va resistant to inactivation by activated protein C. As a result of this resistance, the half- life of Factor Va in plasma is increased, resulting in increased thrombin production and increased risk of thrombosis.

In 1961, Shimomura and Johnson isolated the protein aequorin, and its small molecule cofactor, coelenterazine, from large numbers of Aequorea jellyfish at Friday Harbor Laboratories. They discovered, after initially finding bright luminescence on adding seawater to a purified sample, that calcium ions (Ca2+) were required to trigger bioluminescence. This research also marked the beginning of research into green fluorescent protein which was summarized by Shimomura. In 1967, Ridgeway and Ashley microinjected aequorin into single muscle fibers of barnacles, and observed transient calcium ion-dependent signals during muscle contraction.

Glutathione plays a key role in maintaining proper function and preventing oxidative stress in human cells. It can act as a scavenger for hydroxyl radicals, singlet oxygen, and various electrophiles. Reduced glutathione reduces the oxidized form of the enzyme glutathione peroxidase, which in turn reduces hydrogen peroxide (H2O2), a dangerously reactive species within the cell. In addition, it plays a key role in the metabolism and clearance of xenobiotics, acts as a cofactor in certain detoxifying enzymes, participates in transport, and regenerates antioxidants such and Vitamins E and C to their reactive forms.

In R. sphaeroides, DMSOR is a single-subunit, water- soluble protein that requires no additional cofactors beyond pterin. In E. coli, DMSOR is embedded within the membrane and has three unique subunits, one of which includes the characteristic pterin cofactor, another which contains four 4Fe:4S clusters, and a final transmembrane subunit that binds and oxidizes menaquinol. The transfer of an e- from menaquinol to the 4Fe:4S clusters and finally to the pterin-Mo active site generates a proton gradient used for ATP generation. DMSOR regulated predominantly at a transcriptional level.

Genetically, the structure is encoded by two separate genes (open reading frames) that form an obligate α2β2 heterotetramic complex. The structure was most likely the result of an evolutionary event that caused gene duplication and partial loss of function, since half of the FAD cofactor binding residues are in each gene, and only make a complete binding site when expressed together as a complex. This probably allowed for the substrate binding site to open up considerably to accommodate much larger polycyclic-CoA substrates, rather than fatty acids of varying chain lengths.

A methyl cobalt bond of the intermediary methyl carrier, methlycob(III)alamin is cleaved heterolytically producing cobalamin in its highly reactive oxidation state as cob(I)alamin. The enzyme bound cob(I)alamin cofactor of the MTR enzyme functions as a methyl carrier between 5-MTHF and homocysteine. Cob(I)alamin is oxidised to cob(II)alamin about once every 100 methyl transfer cycles, rendering the cob(I)alamin-MTR-enzyme complex inactive. Reactivation of this enzyme complex occurs through reductive remethylation by MTRR, utilizing S-adenosylmethionine as a methyl donor.

The PHM subunit effects hydroxylation of an O-terminal glycine residue: :peptide-C(O)NHCH2CO2− \+ O2 \+ 2 [H] → peptide-C(O)NHCH(OH)CO2− \+ H2O Involving hydroxylation of a hydrocarbon by O2, this process relies on a copper cofactor. Dopamine beta-hydroxylase, also a copper-containing enzyme, effects a similar transformation. The PAL subunit then completes the conversion, by catalyzing elimination from the hydroxylated glycine: :peptide-C(O)NHCH(OH)CO2− → peptide-C(O)NH2 \+ CH(O)CO2− The eliminated coproduct is glyoxylate, written above as CH(O)CO2−.

Stoichiometric equation representing the metabolism of an aldehyde substrate by ALDH3A1 using NADP+ as a cofactor Electronic excitations of alkene and aromatic functional groups allow certain nucleic acids, proteins, fatty acids and organic molecules to absorb ultraviolet radiation (UVR). Moderate UVR exposure oxidizes specific proteins that eventually serve as signaling agents for an array of metabolic and inflammatory pathways. Overexposure to UVR, on the other hand, can be detrimental to the tissue. In the presence of molecular oxygen, UVR leads to the formation of reactive oxygen species (ROS) that are implicated in many degradation pathways.

Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation (K from koagulation, Danish for "coagulation") or for controlling binding of calcium in bones and other tissues. The complete synthesis involves final modification of these so-called "Gla proteins" by the enzyme gamma- glutamyl carboxylase that uses vitamin K as a cofactor. The presence of uncarboxylated proteins indicates a vitamin K deficiency.

Cofactor engineering most often deals with the manipulation of microorganisms such as Saccharomyces cerevisiae and Escherichia coli, and as such requires the use of recombinant DNA techniques. These techniques utilize small circular segments of DNA called plasmids, which can be introduced and incorporated by microorganisms such as Escherichia coli. These plasmids are specifically designed in labs to be easily incorporated, and affect the expression of various protein, metabolites and enzymes. For instance, a particular plasmid may cause a change in an enzyme's amino acid sequence, which could increase its affinity for a particular substrate.

An alternative example of changing an enzyme’s preference for cofactors is to change NADH dependent reaction to NADPH dependent reactions. In this example, the enzymes themselves are not changed, but instead different enzymes are selected that accomplish the same reaction with the use of a different cofactor. An engineered pathway was created to make 1-butanol from Acetyl-CoA by changing enzymes in the metabolic pathway of S. elongatus. The Clostridium genus is known to produce 1-butanol, providing a pathway that could be inserted in S. elongatus.

Mg2+ binds relatively weakly to these charges, and can be displaced by other cations, impeding uptake and causing deficiency in the plant. Within individual plant cells, the Mg2+ requirements are largely the same as for all cellular life; Mg2+ is used to stabilise membranes, is vital to the utilisation of ATP, is extensively involved in the nucleic acid biochemistry, and is a cofactor for many enzymes (including the ribosome). Also, Mg2+ is the coordinating ion in the chlorophyll molecule. It is the intracellular compartmentalisation of Mg2+ in plant cells that leads to additional complexity.

The remaining subunits in PSII are of low molecular weight (less than 10 kDa), and are involved in PSII assembly, stabilisation, dimerization, and photoprotection. Cytochrome b559, which forms part of the reaction centre core of PSII, is a heterodimer composed of one alpha subunit (PsbE), one beta (PsbF) subunit, and a heme cofactor. Two histidine residues from each subunit coordinate the heme. Although cytochrome b559 is a redox-active protein, it is unlikely to be involved in the primary electron transport in PSII due to its very slow photo-oxidation and photo-reduction kinetics.

This increased binding causes vWD because the high-molecular weight multimers are removed from circulation in plasma since they remain attached to the patient's platelets. Thus, if the patient's platelet-poor plasma is used, the ristocetin cofactor assay will not agglutinate standardized platelets (i.e., pooled platelets from normal donors that are fixed in formalin), similar to the other types of vWD. In all forms of the ristocetin assay, the platelets are fixed in formalin prior to the assay to prevent von Willebrand's factor stored in platelet granules from being released and participating in platelet aggregation.

The O-alkyl cleavage of the ester bond, assisted by an Fe(II) cofactor, creates a carbocation intermediate that is stabilized by the conjugated polyene chain. The delocalization of the carbocation reduces the bond order of the polyene chain, thereby reducing the activation energy of the trans-to-cis isomerization. Phe103 and Thr178 additionally stabilize the isomerized carbocation and are thought to be responsible for the stereoselectivity of the enzyme. After isomerization, a nucleophilic attack by water at C15 restores the conjugation of the polyene chain and completes the ester bond cleavage.

Activated RNA polymerase II transcriptional coactivator p15 also known as positive cofactor 4 (PC4) or SUB1 homolog is a protein that in humans is encoded by the SUB1 gene. The human SUB1 gene is named after an orthologous gene in yeast. SUB1 is induced by oxidative stress, and is involved in coordinating cellular responses to DNA strand breaks that arise after oxidative stressYu L, Ma H, Ji X, Volkert MR. The Sub1 nuclear protein protects DNA from oxidative damage. Mol Cell Biochem. 2016 Jan;412(1-2):165-71.

Crystallographic structure of cytochrome P450 from the bacteria S. coelicolor (rainbow colored cartoon, N-terminus = blue, C-terminus = red) complexed with heme cofactor (magenta spheres) and two molecules of its endogenous substrate epi-isozizaene as orange and cyan spheres respectively. The orange-colored substrate resides in the monooxygenase site while the cyan-colored substrate occupies the substrate entrance site. An unoccupied moonlighting terpene synthase site is designated by the orange arrow. Protein moonlighting (or gene sharing) is a phenomenon by which a protein can perform more than one function.

TMG is an important cofactor in methylation, a process that occurs in every mammalian cell donating methyl groups (–CH3) for other processes in the body. These processes include the synthesis of neurotransmitters such as dopamine and serotonin. Methylation is also required for the biosynthesis of melatonin and the electron transport chain constituent coenzyme Q10, as well as the methylation of DNA for epigenetics. The major step in the methylation cycle is the remethylation of homocysteine, a compound which is naturally generated during demethylation of the essential amino acid methionine.

In mammals, transketolase connects the pentose phosphate pathway to glycolysis, feeding excess sugar phosphates into the main carbohydrate metabolic pathways. Its presence is necessary for the production of NADPH, especially in tissues actively engaged in biosyntheses, such as fatty acid synthesis by the liver and mammary glands, and for steroid synthesis by the liver and adrenal glands. Thiamine diphosphate is an essential cofactor, along with calcium. Transketolase is abundantly expressed in the mammalian cornea by the stromal keratocytes and epithelial cells and is reputed to be one of the corneal crystallins.

3-phosphoglycerate dehydrogenase works via an induced fit mechanism to catalyze the transfer of a hydride from the substrate to NAD+, a required cofactor. In its active conformation, the enzyme's active site has multiple cationic residues that likely stabilize the transition state of the reaction between the negatively charged substrate and NAD+. The positioning is such that the substrate's alpha carbon and the C4 of the nicotinamide ring are brought into a proximity that facilitates the hydride transfer producing NADH and the oxidized substrate. Active site of human PHGDH.

DNA ligase, shown above repairing chromosomal damage, is an enzyme that joins broken nucleotides together by catalyzing the formation of an internucleotide ester bond between the phosphate backbone and the deoxyribose nucleotides. In NHEJ, DNA Ligase IV, a specialized DNA ligase that forms a complex with the cofactor XRCC4, directly joins the two ends. To guide accurate repair, NHEJ relies on short homologous sequences called microhomologies present on the single- stranded tails of the DNA ends to be joined. If these overhangs are compatible, repair is usually accurate.

BBE-like enzymes serve as a catalyzer for a wide range of reactions. All the way from two-electron oxidations as observed in (At)BBE-like 15 to four- electron oxidations as seen in Dbv29. BBE-like enzymes are involved in the synthesis of plenty of isoquinoline alkaloids such as the conversion of (S)-reticuline to (S)-scoulerineAndreas W., Franz H., Toni M. K., Anton G., and Peter M. Biochemical Evidence That Berberine Bridge Enzyme Belongs to a Novel Family of Flavoproteins Containing a Bi-covalently Attached FAD Cofactor. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL.

Methylcobalamin is equivalent physiologically to vitamin B, and can be used to prevent or treat pathology arising from a lack of vitamin B intake (vitamin B12 deficiency). Methylcobalamin is also used in the treatment of peripheral neuropathy, diabetic neuropathy, and as a preliminary treatment for amyotrophic lateral sclerosis. Methylcobalamin that is ingested is not used directly as a cofactor, but is first converted by MMACHC into cob(II)alamin. Cob(II)alamin is then later converted into the other 2 forms, adenosylcobalamin and methylcobalamin for use as cofactors.

Rhodopsin consists of two components, a protein molecule also called scotopsin and a covalently- bound cofactor called retinal. Scotopsin is an opsin, a light-sensitive G protein coupled receptor that embeds in the lipid bilayer of cell membranes using seven protein transmembrane domains. These domains form a pocket where the photoreactive chromophore, retinal, lies horizontally to the cell membrane, linked to a lysine residue in the seventh transmembrane domain of the protein. Thousands of rhodopsin molecules are found in each outer segment disc of the host rod cell.

One mg/dL of phenylalanine is approximately equivalent to 60 μmol/L. A (rare) "variant form" of phenylketonuria called hyperphenylalaninemia is caused by the inability to synthesize a cofactor called tetrahydrobiopterin, which can be supplemented. Pregnant women with hyperphenylalaninemia may show similar symptoms of the disorder (high levels of phenylalanine in blood), but these indicators will usually disappear at the end of gestation. Pregnant women with PKU must control their blood phenylalanine levels even if the fetus is heterozygous for the defective gene because the fetus could be adversely affected due to hepatic immaturity.

An energy deficiency in Schwann cells would account for the disappearance of myelin on peripheral nerves, which may result in damage to axons or loss of nerve function altogether. In peripheral nerves, oxidative enzyme activity is most concentrated around the nodes of Ranvier, making these locations most vulnerable to cofactor deprivation. Lacking essential cofactors reduces myelin impedance, increases current leakage, and slows signal transmission. Disruptions in conductance first affect the peripheral ends of the longest and largest peripheral nerve fibers because they suffer most from decreased action potential propagation.

The blood coagulation and left Factor IX is produced as a zymogen, an inactive precursor. It is processed to remove the signal peptide, glycosylated and then cleaved by factor XIa (of the contact pathway) or factor VIIa (of the tissue factor pathway) to produce a two-chain form, where the chains are linked by a disulfide bridge. When activated into factor IXa, in the presence of Ca2+, membrane phospholipids, and a Factor VIII cofactor, it hydrolyses one arginine-isoleucine bond in factor X to form factor Xa. Factor IX is inhibited by antithrombin. Factor IX expression increases with age in humans and mice.

Among this group are the metal selective deoxyribozymes such as Pb2+-specific 17E, UO22+-specific 39E, and Na+-specific A43. First crystal structure of a DNAzyme was reported in 2016. 10-23 core based DNAzymes and the respective MNAzymes that catalyse reactions at ambient temperatures were described in 2018 and open doors for use of these nucleic acid based enzymes for many other applications without the need for heating. This link and this link describe the DNA molecule 5'-GGAGAACGCGAGGCAAGGCTGGGAGAAATGTGGATCACGATT-3' , which acts as a deoxyribozyme that uses light to repair a thymine dimer, using serotonin as cofactor.

Another factor relatively recently discovered to play a significant role in oceanic primary production is the micronutrient iron. This is used as a cofactor in enzymes involved in processes such as nitrate reduction and nitrogen fixation. A major source of iron to the oceans is dust from the Earth's deserts, picked up and delivered by the wind as aeolian dust. In regions of the ocean that are distant from deserts or that are not reached by dust-carrying winds (for example, the Southern and North Pacific oceans), the lack of iron can severely limit the amount of primary production that can occur.

After receptor binding, Rabies lyssavirus enters its host cells through the endosomal transport pathway. Inside the endosome, the low pH value induces the membrane fusion process, thus enabling the viral genome to reach the cytosol. Both processes, receptor binding and membrane fusion, are catalyzed by the glycoprotein G which plays a critical role in pathogenesis (mutant virus without G proteins cannot propagate). The next step after its entry is the transcription of the viral genome by the P-L polymerase (P is an essential cofactor for the L polymerase) in order to make new viral protein.

Cryptochrome forms a pair of radicals with correlated spins when exposed to blue light. Radical pairs can also be generated by the light- independent dark reoxidation of the flavin cofactor by molecular oxygen through the formation of a spin-correlated FADH-superoxide radical pairs. Magnetoreception is hypothesized to function through the surrounding magnetic field's effect on the correlation (parallel or anti-parallel) of these radicals, which affects the lifetime of the activated form of cryptochrome. Activation of cryptochrome may affect the light-sensitivity of retinal neurons, with the overall result that the animal can sense the magnetic field.

Another way that enzymes can exist in inactive forms and later be converted to active forms is by activating only when a cofactor, called a coenzyme, is bound. In this system, the inactive form (the apoenzyme) becomes the active form (the holoenzyme) when the coenzyme binds. In the duodenum, the pancreatic zymogens, trypsinogen, chymotrypsinogen, proelastase and procarboxypeptidase are converted into active enzymes by enteropeptidase and trypsin. Chymotrypsinogen, is single polypeptide chain of 245 amino acids residues, is converted to alpha-chymotrypsin, which has three polypeptide chains linked by two of the five disulfide bond present in the primary structure of chymotrypsinogen.

This enzyme forms a 45-kDa homodimer of two 22-kDa subunits composed of a core domain and cap domain. The core domain is an α/β Rossmann- like fold containing six antiparallel β-strands surrounded by α-helixes, and it spans residues 1-17 and 77-201 of the amino acid sequence. The cap domain is a 4-helix bundle spanning residues 18-76. The cleft formed by the core and cap domains acts as the enzyme's active site, where three conserved motifs in the core domain plus the cofactor Mg2+ serve as the substrate binding site.

The biosynthetic pathway of the strigolactones has not been fully elucidated, but different steps have been identified, including the required enzymes to carry out the chemical transformation. The first step is the isomerization of the 9th chemical bond of the \beta-carotene, changing from trans configuration to cis. This first step is carried out by the enzyme \beta-carotene isomerase, also called DWARF27 or D27 for short, which required iron as a cofactor. The second step is the chemical separation of 9-cis-\beta-carotene into two different compounds: the first one is 9-cis-aldehyde and the second is \beta-ionone.

In enzymology, diaminopimelate decarboxylase (), also known as diaminopimelic acid decarboxylase, DAPDC, meso-diaminopimelate decarboxylase, DAP- decarboxylase, and meso-2,6-diaminoheptanedioate carboxy-lyase, is an enzyme that catalyzes the cleavage of carbon-carbon bonds in meso 2,6 diaminoheptanedioate to produce CO2 and L-lysine, the essential amino acid. It employs the cofactor pyridoxal phosphate, also known as PLP, which participates in numerous enzymatic transamination, decarboxylation and deamination reactions. This enzyme belongs to the family of lyases, specifically the carboxy-lyases, which cleave carbon-carbon bonds. The systematic name of this enzyme class is meso-2,6-diaminoheptanedioate carboxy- lyase (L-lysine-forming).

Lanthanum acts at the same modulatory site on the GABA receptor as zinc, a known negative allosteric modulator. The lanthanum cation La3+ is a positive allosteric modulator at native and recombinant GABA receptors, increasing open channel time and decreasing desensitization in a subunit configuration dependent manner. Lanthanum is an essential cofactor for the methanol dehydrogenase of the methanotrophic bacterium Methylacidiphilum fumariolicum SolV, although the great chemical similarity of the lanthanides means that it may be substituted with cerium, praseodymium, or neodymium without ill effects, and with the smaller samarium, europium, or gadolinium giving no side effects other than slower growth.

The position of the cofoactors to the active sites on the enzyme are critical to the overall reaction rate thus, any alteration to the cofactor site leads to the disruption of the glucan binding site. Alpha-glucan is also commonly found in bacteria, yeasts, plants, and insects. Whereas the main pathway of α-glucan synthesis is via glycosidic bonds of glucose monomers, α-glucan can be comparably synthesized via the maltosyl transferase GlgE and branching enzyme GlgB. This alternative pathway is common in many bacteria, which use GlgB and GlgE or the GlgE pathway exclusively for the biosynthesis of α-glucan.

Thiamine serves several indispensable roles in the brain that affect cognitive function either directly or indirectly. It is a functional component of neuronal and microglial cell membranes, and serves as a modulator of the acetylcholine neurotransmitter system. Thiamine indirectly drives cognitive processes as a necessary cofactor in the pathways needed to synthesise fatty acids, steroid hormones, nucleic acids and precursory molecules for various compounds involved in brain function. It has been shown that cats suffer irreversible brain damage when deprived of thiamine that hinders memory and learning even after thiamine has been reintroduced to the diet.

Recently, a second parallel protective pathway was independently discovered by two labs that involves the oxidoreductase FSP1/AIFM2. Their findings indicate that FSP1/AIFM2 enzymatically reduces non- mitochondrial Coenzyme Q10, thereby generating a potent lipophilic antioxidant to suppresses the propagation of lipid peroxides. A similar mechanism for a cofactor moonlighting as a diffusable antioxidant was discovered in the same year for tetrahydrobiopterin/BH4, a product of the rate limiting enzyme GCH1. Human prostate cancer cells undergoing ferroptosis Small molecules such as erastin, sulfasalazine, sorafenib, altretamine, RSL-3, ML-162 and ML-210 are known inhibitors of this tumor cell growth and induce ferroptosis.

A ternary complex is a protein complex containing three different molecules that are bound together. In structural biology, ternary complex can also be used to describe a crystal containing a protein with two small molecules bound, for example cofactor and substrate; or a complex formed between two proteins and a single substrate. In Immunology, ternary complex can refer to the MHC–peptide–T-cell-receptor complex formed when T cells recognize epitopes of an antigen. Some other example can be taken like ternary complex while eukaryotic translation, in which ternary complex is composed of eIF-3 & eIF-2 + Ribosome 40s subunit+ tRNAi.

Folic acid (FA, folate or vitamin B9), is a vital nutrient required by all living cells for nucleotide biosynthesis and for the proper metabolic maintenance of 1-carbon pathways. Aside from its cofactor role for intracellular enzymes, FA also displays high affinity for the folate receptor (FR), a glycosylphosphatidyinositol-linked protein that captures its ligands from the extracellular milieu and transports them inside the cell via a non-destructive, recycling endosomal pathway. The FR is also a recognized tumor antigen/biomarker. Because of this, diagnostic and therapeutic methods which exploit the FR's function are being developed for cancer.

Around this time, the first functional studies of prostasomes were also performed. Cancerous prostate cells and prostate cells with low differentiation continue to produce and secrete prostasomes. Possibly, the high incidence of prostate cancer in elderly men could be due to the immunomodulatory properties of prostasomes, protecting the cancer from attack by the immune system. Immune regulating proteins found in prostasomes include: amino-peptidase N (CD13); dipeptidyl-peptidase IV (CD26); enkephalinase (neutral endopeptidase, CD10); angiotensin converting enzyme (ACE, CD143); tissue factor TF (CD142, thromboplastin); decay accelerating factor (CD55); protectin (CD59, inhibitor of MAC) and complement regulatory membrane cofactor protein (CD46).

1-4-dihydroxy-2-napthoate polyprenyltransferase is the 8th out of 9 steps in the biosynthesis of menaquinone (Vitamin K), specifically -9 within ecoli. Vitamin K is a cofactor vital for living and functions as one electron transporter in photosynthesis as a redox molecule. The reactions this enzyme catalyzes works by taking the soluble bicyclic naphthalenoid compound DHNA and converting it into -9 by attaching a 40 carbon side chain to DHNA. However this enzyme is unique in the sense that it can put different lengths of carbon side chains onto DHNA to produce different and menaquinols.

Catechol 1,2- dioxygenase (, 1,2-CTD, catechol-oxygen 1,2-oxidoreductase, 1,2-pyrocatechase, catechase, catechol 1,2-oxygenase, catechol dioxygenase, pyrocatechase, pyrocatechol 1,2-dioxygenase, CD I, CD II) is an enzyme that catalyzes the oxidative ring cleavage of catechol to form cis,cis-muconic acid: Figure 1. The overall reaction of catechol 1,2-dioxygenase. Using a non- heme iron(III) complex, 1,2-CTD is able to oxidatively cleave catechol into cis,cis-muconic acid. More specifically, 1,2-CTD is an intradiol dioxygenase, a family of catechol dioxygenases that cleaves the bond between the phenolic hydroxyl groups of catechol using an Fe3+ cofactor.

Thiamine in the human body has a half-life of 18 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine, thiamine pyrophosphate (TPP), is a cofactor involved in the citric acid cycle, as well as connecting the breakdown of sugars with the citric acid cycle. The citric acid cycle is a central metabolic pathway involved in the regulation of carbohydrate, lipid, and amino acid metabolism, and its disruption due to thiamine deficiency inhibits the production of many molecules including the neurotransmitters glutamic acid and GABA. Additionally thiamine may also be directly involved in neuromodulation.

Summary of heme B biosynthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow) Ferrochelatase catalyzes the insertion of ferrous iron into protoporphyrin IX in the heme biosynthesis pathway to form heme B. The enzyme is localized to the matrix-facing side of the inner mitochondrial membrane. Ferrochelatase is the best known member of a family of enzymes that add divalent metal cations to tetrapyrrole structures. For example, magnesium chelatase adds magnesium to protoporphyrin IX in the first step of bacteriochlorophyll biosynthesis. Heme B is an essential cofactor in many proteins and enzymes.

BPV-4 causes squamous cell carcinomas of the alimentary tract, and BPV-1/2 causes carcinomas and haemangioendotheliomas of the urinary bladder, in both cases in animals that have fed on bracken (Pteridium aquilinum). Such cancers are common in locations where grazing land is infested with bracken, such as the western Scottish Highlands, southern Italy and the Nasampolai Valley in Kenya. Bracken contains several immunosuppressants and mutagens, including quercetin and ptaquiloside. Consumption of large quantities by cattle leads to an acute poisoning syndrome with symptoms of bone marrow depletion, while at lower levels of long-term consumption it acts as a cancer cofactor.

EGF- CFC proteins are membrane bound extracellular factors that serve as essential cofactor in Nodal signaling and in vertebrate development as a whole. This family of cofactors includes One-eyed Pinhead (oep) in Zebrafish, FRL1 in Xenopus, and Cripto and Criptic in mouse and human. Genetic studies of oep in zebrafish have shown that the knockout of both maternal and zygotic oep leads to a phenotype similar to that of the squint/Cyclops (nodals) knockout. Similarly, over-expression of either the nodal (squint/Cyclops) or oep with the knockout of the other does not show phenotypical differences.

The cofactor TPP, C12 H18 N4 O7 P2 S, is needed for this reaction's mechanism; it acts as the prosthetic group to the enzyme. The carbon atom between the sulfur and nitrogen atoms on thiazole ring act as carbanion which binds to the pyruvate. TPP has an acidic H+ on its C2 that acts as the functional part of the thiazolium ring; the ring acts as an "electron sink", enabling the carbanion electrons to be stabilized by resonance. The TPP can then act as a nucleophile with the loss of this C2 hydrogen, forming the ylide form of TPP.

A large number of iron-sulfur cluster-containing enzymes cleave SAM-e reductively to produce a 5′-deoxyadenosyl 5′-radical as an intermediate, and are called radical SAM enzymes. Most enzymes with this capability share a region of sequence homology that includes the motif CxxxCxxC or a close variant. The radical intermediate allows enzymes to perform a wide variety of unusual chemical reactions. Examples of radical SAM enzymes include spore photoproduct lyase, activases of pyruvate formate lyase and anaerobic sulfatases, lysine 2,3-aminomutase, and various enzymes of cofactor biosynthesis, peptide modification, metalloprotein cluster formation, tRNA modification, lipid metabolism, etc.

The oxidation occurs through the TET (Ten-eleven translocation) family dioxygenases (TET enzymes) which can convert 5mC, 5hmC, and 5fC to their oxidized forms. However, the enzyme has the greatest preference for 5mC and the initial reaction rate for 5hmC and 5fC conversions with TET2 are 4.9-7.6 fold slower. TET requires Fe(II) as cofactor, and oxygen and α-ketoglutarate (α-KG) as substrates, and the latter substrate is generated from isocitrate by the enzyme isocitrate dehydrogenase (IDH). Cancer however can produce 2-hydroxyglutarate (2HG) which competes with α-KG, reducing TET activity, and in turn reducing conversion of 5mC to 5hmC.

The lipophilic diacylglycerol remains in the membrane, acting as a cofactor for the activation of protein kinase C. These receptors are also associated with Na+ and K+ channels. Their action can be excitatory, increasing conductance, causing more glutamate to be released from the presynaptic cell, but they also increase inhibitory postsynaptic potentials, or IPSPs. They can also inhibit glutamate release and can modulate voltage-dependent calcium channels. Group I mGluRs, but not other groups, are activated by 3,5-dihydroxyphenylglycine (DHPG), a fact that is useful to experimenters because it allows them to isolate and identify them.

There is an increasing trend of using ICP-MS as a tool in speciation analysis, which normally involves a front end chromatograph separation and an elemental selective detector, such as AAS and ICP-MS. For example, ICP-MS may be combined with size exclusion chromatography and quantitative preparative native continuous polyacrylamide gel electrophoresis (QPNC-PAGE) for identifying and quantifying native metal cofactor containing proteins in biofluids. Also the phosphorylation status of proteins can be analyzed. In 2007, a new type of protein tagging reagents called metal-coded affinity tags (MeCAT) were introduced to label proteins quantitatively with metals, especially lanthanides.

One of these enzymes is a radical SAM, a family of enzymes often associated with C—X bond- forming reactions (X = S, N). This intermediate pyranopterin is then converted to the molybdopterin via the action of three further enzymes. In this conversion, the enedithiolate is formed, although the substituents on sulfur remain unknown. Sulfur is conveyed from cysteinyl persulfide in a manner reminiscent of the biosynthesis of iron-sulfur proteins. The monophosphate is adenylated (coupled to ADP) in a step that activates the cofactor toward binding Mo or W. These metals are imported as their oxyanions, molybdate, and tungstate.